NIH Publication No. 03-5446

October 2003
Our Challenge Goal to the Nation 

due to cancer by 2015. 

Eliminate the suffering and death 
The Nation’s Investment in 

Cancer Research


U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES 

National Institutes of Health 

A Plan and Prepared by 

Budget Proposal the Director 

for Fiscal Year National Cancer Institute 

2005 
Each year, as mandated by the National Cancer Act of 1971 (P.L. 92-218), the 

National Cancer Institute (NCI) prepares a plan for building on research successes, 

supporting the cancer research workforce with the technologies and resources it 

needs, and ensuring that research discoveries are applied to improve human health. 

This annual plan and budget proposal is provided directly to the President of the 

United States for formulating the budget request to Congress. This document is also 

used by NCI staff; the researcher community; professional organizations; advisory 

groups; cancer information, education, and advocacy organizations; and public and 

private policy makers. It is our hope that this document will inspire all who read it 

to join the fight against cancer. 
Director’s Message


Several months ago, I attended a town hall meeting of the President’s Cancer Panel, where I had the good 

fortune to meet a brave little boy named Dakoda. He had recently been diagnosed with an inoperable brain 

tumor. Due to start chemotherapy later that night, he came to the meeting with his father, mother, and younger 

sister. His father, in a voice trembling with emotion, described the challenges of his son’s illness and 

emphasized the progress he was making in his treatment. He also talked about the family’s commitment to 

defeating Dakoda’s cancer and encouraged those of us at the meeting that day to rededicate our efforts to 

develop new and more effective cancer therapies. Dakoda’s story embodies universal themes of courage, 

commitment, and inspiration. Such stories — of the suffering that patients and their families endure on a 

daily basis because of this disease — remind us of the great value of cancer research and reinforce our 

determination to achieve our goal of eliminating the suffering and death due to cancer. 

In 1971 — with the passage of the National Cancer Act – we committed our national will and resources to eliminating cancer. A cure for this complex set of diseases has 

proven far more elusive than anticipated thirty-three years ago. Yet our persistence 

and patience have led to increasingly significant dividends. There are now nearly ten 

million cancer survivors in the United States compared to three million in 1971. Death 

rates from the four most common cancers — lung, breast, prostate, and colorectal – 

continue to decline. Over the past decade, Americans have experienced a 7 percent 

decline in mortality from cancer and hundreds of thousands of lives have been saved. 

As this document illustrates, we are making extraordinary progress in cancer research. 

This progress has opened new avenues to even greater opportunities that will enable 

us to reach our goal of eliminating the suffering and death due to cancer. 

To achieve this goal, we must continue to nurture the investment in infrastructure 

and intellectual capital that we began over three decades ago. The passage of the 

National Cancer Act challenged our Nation in 1971 and motivated many of our 

Nation’s best and brightest to devote their professional lives to the study of cancer in 

all its formidable complexity. Only during the past decade have we amassed sufficient understanding of cancer’s genetic, molecular, and cellular puzzle to elucidate the 

mechanisms responsible for its initiation and progression. We are now engaged in the 

development of extraordinary interventions directed at the specific processes 

governed by those mechanisms. We have at last entered into an exponential phase of 

progress in which scientific research, fueled by previously unimagined technologies, 

permits us to envision a future when people can live with, and not die from, cancer. 

While we may not cure cancer in the short term, we will develop the knowledge and 

tools to preempt its progression and thereby, effectively reduce its burden on our 

society. Using this strategy, we can and will prevent, detect, eliminate, and control 

individual cancers, and we must work together to accomplish this by 2015. 

In this professional judgment budget, we at the National Cancer Institute highlight 

our vision for progress on the road ahead. The National Cancer Act of 1971 

started us on this journey — and we must build on that momentum to persevere, to 

rapidly accelerate our pace, and to reach new heights of progress. Dakoda and his 

family, like all the families of America, are depending on the National Cancer 

Institute — and the entire cancer research community — to eliminate the suffering 

and death due to cancer by 2015. We will not fail! 

DIRECTOR’S MESSAGE 

A Plan and Budget Proposal for Fiscal Year 2005 iii 

Table of Contents


iii Director’s Message 

vi Executive Summary 

xii Highlights of Progress 

1 Our Action Plan for Fiscal Year 2005 

4 Budget Request for Fiscal Year 2005 

6 Disease-Specific Research 

9 Broad Research Priorities 

Core Scientific Areas 

10 Genes and the Environment 

16 Signatures of the Cancer Cell and Its Microenvironment 

24 Molecular Targets of Prevention, Diagnosis, and Treatment 

31 Cancer Imaging and Molecular Sensing 

Areas of Public Health Emphasis 

38 Research on Tobacco and Tobacco-Related Cancers 

45 Optimizing Energy Balance to Reduce the Cancer Burden 

51 Improving the Quality of Cancer Care 

58 Reducing Cancer-Related Health Disparities 

64 NCI and NIA Launch New Efforts on Aging and Cancer 

66 Cancer Survivorship: Optimizing Health and Quality of Life after Cancer 

72 Platforms for Discovery, Development, and Delivery 

73 Enhancing Investigator-Initiated Research 

79 Transforming the Capacity of Centers, Networks, and Consortia 

86 National Clinical Trials Program in Treatment and Prevention 

93 NCI Intramural Research Program Provides a Platform for 

Innovation, Translation, and Application 

94 Enablers of Discovery, Development, and Delivery 

95 Bioinformatics 

99 Cancer Communications 

Spotlights 

30 Quality Patient Care Includes Radiation Oncology 

37 Cancer Advocates Help Put a Human Face on Cancer Research 

78 NCI Addresses Obstacles to New Treatments for Pediatric Cancer 

84 NCI Partners to Advance Cancer Research 

22 Story of Discovery 

Anti-Inflammatory Therapeutics May Provide Secondary Benefits for Cancer 

People’s Stories 

40 Tobacco-Related Cancers in Women 

50 Energy In, Energy Out – A Critical Balance 

55 Improving Quality of Life for Patients and Their Caregivers 

TABLE OF CONTENTS 

A Plan and Budget Proposal for Fiscal Year 2005 v 
Executive Summary


In 2001, the National Cancer Institute (NCI) issued the nationwide cancer community this Challenge Goal: 

To eliminate the suffering and death due to cancer by 2015. Never before have so many scientific tools and 

technologies and so much biomedical knowledge been assembled to power our ability to reach our 

Challenge Goal. We are experiencing exponential growth in our knowledge of cancer, growth fueled by 

historically high levels of funding, scientific expertise, infrastructure, and enabling technologies. With a sharp 

focus on our goal and continued budgetary support, we can harness advances in discovery and development research to deliver interventions for preventing cancer; detecting it early; and slowing, stopping, or 

reversing its progression to a lethal phenotype. 

Our success will depend on our ability to integrate our activities, from the 

discovery of new scientific knowledge, to the development of new interventions, 

to the delivery of evidence-based interventions for all who need them. We must 

work to remove the major barriers that impede progress and ensure that all 

new activities are informed by past lessons learned. Most importantly, we must 

maintain our momentum so that the progress we have made thus far turns into 

the promise of a better future for those with, or at risk for, cancer. 

As the leader of the National Cancer Program, NCI provides vision and direction 

to the nationwide community of researchers, public health workers, healthcare 

providers, patients, advocates, and policymakers working to defeat cancer. Our 

budget has historically reflected this crucial role. NCI’s total proposed Fiscal Year 

2005 Budget Request is $6,211,000,000. This represents an increase of 

$1,440,481,000 over the Fiscal Year 2004 President's Budget. Of this increase, 

$329,480,000 will allow us to continue our commitments into 2005 (Core 

Budget). An additional $471,500,000 will be used for new and expanded work 

in broad research priority areas, with a focus on optimizing opportunities for 

intervention development and delivery. An increase of $555,201,000 will allow 

for additional support to our major research infrastructures or platforms: 

investigator-initiated research; centers, networks, and consortia; and clinical trials. And $84,300,000 will be used to improve and expand cancer bioinformatics 

and communications tools and approaches to enable precise and accelerated 

research and ensure the translation of discovery to new intervention development 

and delivery. 

DISEASE-SPECIFIC RESEARCH 

“Cancer” is not one but actually more than 100 distinct diseases. We are learning 

that many disease sites have cancer subtypes with unique molecular characteristics 

that influence how they develop and progress and how they can be effectively prevented, detected, and treated. NCI continues to work with cancer research and 

advocacy communities to identify and address needs for work in specific types of 

cancer. This year, a Sarcoma Progress Review Group is under way, and NCI diseasespecific working groups continue their efforts to follow up on recommendations of 

other Progress Review Groups convened over the past several years. This kind of 

disease-specific focus is integral to achieving our Challenge Goal. 

vi The Nation’s Investment in Cancer Research 
BROAD RESEARCH PRIORITIES 

NCI’s action plan for achieving our Challenge Goal includes ongoing research in 

four core scientific areas and five areas of public health emphasis. Identified with 

assistance from our advisory boards, the larger research community, and the 

cancer advocacy community, we believe investment in these areas will allow us 

to accelerate the pace of discovery and optimize the use of existing and new 

knowledge for the development and delivery of evidence-based interventions. 

Core Scientific Areas Genes and the Environment. Cancer research has benefited enormously from 

increasingly sophisticated molecular technologies and the resources generated by 

As we more fully understand the mapping of the human genome. Scientists have a better understanding of the 

cancer-related molecular, complexity of genetic and environmental interactions that lead to cancer devel­ cellular, microenvironment, 

behavioral, psychological, opment. To build on this understanding, NCI must continue to develop novel 

and social influences, we ways to study the complexities of genetic and environmental contributions to cancer. 

can develop more effective With 2005 funding increases, we will place special emphasis on large-scale and less harmful approaches interdisciplinary studies to help scientists uncover environmental risk factors, to cancer prevention, 


early detection, diagnosis, identify genetically susceptible individuals, develop appropriate interventions and


treatment, and control. precautions for people at high risk, and generate new individual and public health


strategies to avoid adverse environmental or lifestyle-related exposures. 

Signatures of the Cancer Cell and Its Microenvironment. Cancer is not a self-contained collection of malignant cells but rather is integrally associated with its 

tumor microenvironment, which includes a variety of cell types that are often 

altered through interaction with cancer cells. Both cancer cells and their surrounding environment need to be fully characterized in order to understand how 

cancer grows in the body, and both need to be considered when developing new 

interventions to fight the disease. Scientists are deciphering the “signatures” (signals of the presence of cancer) of cancer cells and cells in the microenvironment. 

Continued investments will be required in 2005 to sustain progress toward defining the full range of molecular signatures for cancer and understanding 

how interactions among cancer cells and the microenvironment lead to tumor 

development and metastasis. 

Molecular Targets of Prevention, Diagnosis, and Treatment. As we more fully 

understand the molecular causes of cancer and its development and progression, 

we can use that information to discover, develop, and deliver agents that specifically “target” these causes. Such molecularly targeted interventions have the 

potential to dramatically improve the prevention, diagnosis, and treatment of 

cancer. In 2005, we must expand our efforts to identify, characterize, and validate 

the combinations of cellular proteins and pathways that cause cancer. And we 

must significantly increase the number of highly effective cancer interventions 

that are directed at validated targets. 

Cancer Imaging and Molecular Sensing. Cancer research and care are both critically dependent on imaging technologies. Imaging advances are already permitting 

A Plan and Budget Proposal for Fiscal Year 2005 

EXECUTIVE SUMMARY 

vii 
Areas of Public 

Health Emphasis 

In each priority area, we 

need better science to 

understand the complexities, 

and there is a pressing need 

to address the challenges 

posed to our Nation’s healthcare system by the rising 

incidence of cancer in the 

aging U.S. population. 

remarkable accuracy in detecting whether a tumor has invaded vital tissue, grown 

around blood vessels, or spread to distant organs; allowing physicians to monitor 

patient progress without the need for biopsies; and allowing precise delivery of various tumor-destroying approaches. With sufficient resources in 2005, NCI will 

build on this momentum by expanding the discovery and development of novel 

imaging agents, devices, and methods; accelerating the integration of advanced 

imaging methods into therapeutic clinical trials; speeding the development and 

clinical testing of image-guided interventions (IGI); and stimulating research on 

components and systems integration of devices for in vivo molecular sensing. 

Research on Tobacco and Tobacco-Related Cancers. Tobacco use is the leading 

preventable cause of illness and death in the United States and is scientifically 

linked to an increasing number of cancers. Two obstacles that confront the 

research community in the fight against tobacco-related disease are particularly 

complex and drive the research agenda in this area: the addicting nature of tobacco products and the impact of tobacco advertising and marketing, especially on 

adolescents. In 2005, with sufficient resources, NCI will lead a vigorous research 

and public health effort consistent with the enormous burden of tobacco-related 

disease. We will support and develop innovative, integrated studies and interventions to understand, prevent, and treat tobacco use and addiction. And we will 

work to deliver those interventions to aid in the prevention and treatment of 

tobacco use and tobacco-related cancers, and to inform public health policy. 

Optimizing Energy Balance to Reduce the Cancer Burden. International teams of 

scientists have assembled compelling evidence that overweight and obesity, as 

well as low levels of physical activity, increase the risk of developing many cancers. At a time when almost two-thirds of the U.S. population is overweight or 

obese, NCI plans to invest additional resources into research on energy balance 

and carcinogenesis and into the development of related interventions for cancer 

prevention and control. Sufficient resources in 2005 will enable NCI to initiate 

new research to discover how body weight, physical activity, and diet, along 

with genetic and environmental factors, interact over a lifetime to influence the 

cancer process. We will also strive to improve cancer-related health outcomes by 

accelerating research on energy balance-related behaviors and by developing 

interventions across diverse populations. 

Improving the Quality of Cancer Care. Far too few U.S. cancer patients receive 

the highest caliber of cancer care. At the same time, experts often differ substantially on what constitutes optimal care, especially from the patient’s perspective, 

and on the best approaches for improvement. NCI plays a vital role in nationwide 

efforts to improve cancer care quality. With increased funding in 2005, we will 

further enhance quality-of-care research within and beyond the NCI clinical 

trials program. We will work to incorporate symptom management and palliative 

care into the full spectrum of cancer quality improvement research and translation efforts. We will sponsor collaborative projects to identify, develop, and 

monitor progress on core measures of cancer care quality and to translate 

viii The Nation’s Investment in Cancer Research 
research evidence into better quality care. And we will strengthen the methodological and empirical foundations of cancer care quality assessment as well as 

the measures that are used in those assessments. 

Reducing Cancer-Related Health Disparities. The scientific community has a critical and unique role in addressing the moral and ethical dilemmas posed by the 

unequal burden of cancer in our society. We know that complex interactions 

among genetic susceptibilities and the risks imparted by individual and group 

behaviors, age, and social and environmental circumstances determine health 

throughout an individual’s life span, including who becomes ill, who survives disease, and who maintains good quality of life after diagnosis and treatment. In 

2005, NCI will use increased resources to work with other agencies in the 

Department of Health and Human Services (HHS) to implement recommendations from the Trans-HHS Cancer Health Disparities Progress Review Group, 

convened in 2003. We will continue discovery efforts to more fully define the 

magnitude and causes of health disparities in cancer while emphasizing the translation of what we know today into the development and delivery of effective 

interventions to reduce cancer health disparities in all populations. 

Improving Treatment Outcomes and Quality of Life for Cancer Survivors. 

Although cancer survivors are living longer, more productive lives than ever 

before, they are not yet free from the adverse effects of cancer diagnosis and treatment. NCI is working collaboratively with other groups to conduct the research 

that will help cancer survivors enjoy an improved quality of life. We plan to use 

increased resources in 2005 to discover the biological, physical, psychological, 

and social mechanisms, and their interactions, that affect a cancer patient's 

response to disease, treatment, and recovery. We will also accelerate the development of intervention research in these areas and collaborate with others 

to ensure the delivery of new information, interventions, and best practices to 

relevant audiences. And we will expand the development and use of tools to 

assess health-related quality of life and quality of care of post-treatment cancer 

survivors and their families. 

PLATFORMS FOR DISCOVERY, DEVELOPMENT, AND DELIVERY 

Bringing the benefits of can- Enhancing Investigator-Initiated Research 

cer research to the American Investigator-initiated research has always been the primary means by which bio- people depends on building 

and sustaining the strong medical research is funded and conducted. These investigators ask the critical 

research mechanisms, sup- questions, explore the options, develop and test innovative technologies, and 

port structures, and collabo- make the discoveries that lead to better cancer science and its application to rations that make it possible patient care. With additional resources in 2005, we will be able to increase fund- for us to pursue rapidly 

evolving discoveries. ing for, and the numbers of, competing research grants and provide incentives for 

transdisciplinary and collaborative research. We will also apply resources to 

encourage investigators to commit to careers in cancer research, to propose more 

innovative and higher-reward projects, and to conduct research in priority areas 

identified by advisory committees, NCI staff, and Progress Review Groups. 

EXECUTIVE SUMMARY 

A Plan and Budget Proposal for Fiscal Year 2005 ix 
Transforming the Capacity of Centers, Networks, and Consortia. The interdisciplinary nature of today’s cancer research requires new infrastructures that support 

team science and enable the sharing of a multitude of resources. The centers, networks, and consortia created and supported by NCI over the past 10 years comprise a model framework upon which to “grow” this evolving paradigm. In 2005, 

we will use increased resources to promote the strategic growth of NCI-supported 

Cancer Centers, incorporating and realigning resources to accelerate discovery, 

development, and delivery. We will promote collaborations to improve access of 

minority populations to state-of-the-art clinical and population studies, cancer 

treatments, technologies, and care. And we will expand the capacity of NCI centers, networks, and consortia to engage in newly developing areas of research and 

technology and to act as platforms for translating discoveries into interventions. 

National Clinical Trials Program. NCI-supported clinical trials provide a crucial 

infrastructure for moving new cancer interventions from the laboratory to studies in 

people with, or at risk for, cancer and then to the healthcare setting. We help 

researchers from public, industrial, and academic settings develop anti-cancer agents 

for a broader array of tumor types and at a faster pace than would otherwise be possible. While much has been accomplished to streamline cancer clinical trials, NCI 

must further accelerate movement of promising research discoveries into clinical 

development and delivery to the public. In 2005, NCI will use increased funding 

towards identifying and accelerating development of the most promising new agents 

for cancer treatment and prevention; strengthening scientific planning and leadership for large clinical trials; doubling the rate at which Phase III trials are completed; and ensuring that clinical trials are broadly accessible to cancer patients, 

populations at risk for cancer, and the physicians who care for these groups. 

NCI’s Intramural Research Program. NCI’s Intramural Research Program (IRP) 

provides a unique venue for research innovation, translation, and application. The 

IRP serves as a proving ground for long-term, high-risk/high-impact projects. It 

complements our robust Extramural Research Program, which distributes about 

three-quarters of our research funding to research sites around the country. The 

opening of the new NIH Clinical Center facility in 2004, the establishment of new 

consortia linking extramural and intramural investigators, the development of new 

technologies, and new efforts to foster interdisciplinary approaches to scientific discovery will strengthen the work of NCI’s IRP and its unique contributions to 

helping us meet our Challenge Goal to eliminate suffering and death due to cancer. 

ENABLERS OF DISCOVERY, DEVELOPMENT, AND DELIVERY 

Making these and other Bioinformatics. The exponential expansion of biomedical knowledge is generatbioinformatics tools available ing a tidal wave of data. Contemporary bioinformatics tools must be harnessed to the research community 

for analysis and resource to support cancer research and care, as well as effective dissemination of inforsharing is vital for enabling mation to patients. NCI is positioned to provide the kind of informatics system 

investigators to carry out and analytic tools needed to integrate diverse data types, capture and share state-of-the-art studies. research outcome data, and provide user-friendly tools that permit patients and 

x The Nation’s Investment in Cancer Research 
Larger investments in cancer 

communications will enable 

the translation of successful 

intervention research into 

practice. 

their advocates to interact more directly with the cancer research community. 

With sufficient resources in 2005, we will establish a network of information 

technology partners and support the development of a shared infrastructure and 

tools that facilitate data mining and data integration. 

Cancer Communications. Significant barriers impede the flow of effective cancer 

communications to patients and their caregivers, underserved populations, advocacy groups, health professionals, and the public health community. NCI strives to 

understand, apply, and disseminate effective communication approaches that maximize access to and appropriate use of cancer information by all who need it. In 2005, 

we will use funding in this area to increase knowledge about cancer information 

needs, beliefs, decisionmaking processes, and behaviors; develop and evaluate communication resources and interventions for reducing the cancer burden, particularly 

among underserved populations; and engage with partners and the media to deliver 

evidence-based cancer interventions in clinical and public health programs. 

(dollars in thousands) 

$4,770,519 

329,480 

Core Scientific Areas 

73,150 

35,300 

47,650 

Cancer Imaging and Molecular Sensing 44,750 

Areas of Public Health Emphasis 

75,000 

57,800 

36,300 

71,300 

Cancer Survivorship: Optimizing Health and Quality of Life after Cancer 30,250 

471,500 

123,501 

96,800 

334,900 

555,201 

Bioinformatics 40,800 

Cancer Communications 43,500 

84,300 

$6,211,000 

EXECUTIVE SUMMARY 

NCI’s Budget Request for Fiscal Year 2005 

Fiscal Year 2004 President’s Budget 

Increase to Core Budget 

Broad Research Priorities 

Genes and the Environment 

Signatures of the Cancer Cell and Its Microenvironment 

Molecular Targets of Prevention, Diagnosis, and Treatment 

Research on Tobacco and Tobacco-Related Cancers 

Optimizing Energy Balance to Reduce the Cancer Burden 

Improving the Quality of Cancer Care 

Reducing Cancer-Related Health Disparities 

Subtotal Broad Research Priorities 

Platforms for Discovery, Development, and Delivery 

Enhancing Investigator-Initiated Research 

Transforming the Capacity of Centers, Networks, and Consortia 

National Clinical Trials Program in Treatment and Prevention 

Subtotal Platforms for Discovery, Development, and Delivery 

Enablers of Discovery, Development, and Delivery 

Subtotal Enablers of Discovery, Development, and Delivery 

Total FY 2005 Budget Request 

A Plan and Budget Proposal for Fiscal Year 2005 xi 
The Annual Report to the Nation on the Status of Cancer 1975-2000, Featuring the 

Uses of Surveillance Data for Cancer Prevention and Control1 was released in 

September 2003. The report shows that overall, cancer death rates neither increased 

nor decreased from 1998 to 2000, and cancer incidence rates were stable from 1995 

rectal, breast, and prostate) continued to decline. Researchers believe the drop in 

lung cancer mortality reflects similar declines in tobacco smoking. Improvements in 

breast cancer incidence and mortality rates appear to result from increased use of 

attention to some worsening cancer health disparities. For example, a growing difference in death rates between White and Black populations for colorectal and 

breast cancers suggests that Black men and women may not have experienced the 

same benefits from screening and treatment services as their White counterparts. In 

addition, higher rates of late-stage breast cancer in some population groups and 

geographic areas may reflect delayed access to care, often among women who lack 

health insurance and among recent immigrants. The report concludes that further 

reductions in cancer incidence and death rates will require strong Federal, state, 

local, and private partnerships to apply evidence-based control measures, improve 

the delivery of quality cancer care, and develop more effective screening strategies 

that reach all segments of the population. 

Discovery 

May Be Reversed by Smoking or Drinking 

While exploring possible anti-cancer effects of beta carotene as a dietary supplement, NCI-supported researchers discovered that people taking the supplements 

who also smoke cigarettes and/or regularly consume alcohol tended to have an 

clinical trial exploring the relationship among beta carotene supplementation, 

smoking and drinking behaviors, and the recurrence of colon polyps, a precursor 

decreased the recurrence of polyps in the study population among patients who neither smoke nor consume alcohol. In contrast, beta carotene supplementation slightly increased the risk of polyp recurrence in people who smoke or consume one or 

study which showed that beta carotene increased the risk of melanoma in smokers 

but not in nonsmokers. This varying effect of beta carotene supplementation on 

xii 

“As a nurse, I see a lot of the 

cost of cancer in the faces of 

my patients and their loved 

to want to see our Nation 

One in four deaths in the United States is attributable to cancer, and one in three Americans will eventually 

develop some form of cancer. Each day, 3,400 people in America are diagnosed with cancer and another 1,500 

die from the disease. But the burden of cancer is too often greater for the poor, ethnic minorities, and the 

uninsured than for the general population. 

Mortality from Four Leading Cancers Continues to Decline, 

but Some Cancer Disparities Are Increasing 

to 2000. However, mortality rates of the four most common cancers (lung, colomammography and the availability of improved therapies. Yet, the report also calls 

Protective Effect of Beta Carotene on Colorectal Cancer Risk 

increased risk of developing lung cancer. They reported recent findings from a large 

condition to colorectal cancer. Beta carotene supplementation substantially 

more alcoholic beverages a day, with the greatest risk elevation seen in people who 

both smoke and drink regularly. These findings are similar to those of a previous 

The Nation’s Investment in Cancer Research 

Highlights of Progress 

ones. That’s enough for me 

support cancer research. 

I want to see the suffering 

erased from every face, no 

matter who they are, what 

they look like, or where they 

come from.” 
cancer risk, depending on patient behaviors, suggests the need for caution in choosing cancer prevention interventions for general use, especially when mechanisms of 

action and interactions with other lifestyle factors have not been clearly defined. 

While researchers increasingly discover genetic and environmental risk factors for 

many types of cancers, the causes of brain tumors in adults remain poorly undergenetic disorders, account for only a small number of brain tumors. In a recent 

— 

those that code for proteins that help break down harmful chemicals such as 

solvents, pesticides, and ethanol — may affect brain tumor risk. These researchers 

tested the blood of nearly 800 adult brain tumor patients, and a similar number of 

control patients, for genetic polymorphisms in two such genes, GST and CYP2, that 

have been implicated in brain tumor risk. A number of the polymorphisms were 

indeed associated with the development of brain tumors. If these findings are validated in other studies of a similar scale, the next step would be to pool samples from 

multiple epidemiological studies and examine interactions of genotypes with 

specific occupational exposures. Defining the risk of brain tumor development by 

specific gene/environment interactions will help the cancer community to identify 

appropriate interventions and precautions for people at high risk. 

2 

consumption of animal fat and red meat, and low consumption of fruits and vegetables. Even so, the etiology of prostate cancer remains largely unknown. Since 

farming is the most consistent occupational risk factor for this disease, scientists 

have been seeking to clarify the potential risks associated with pesticide use. 

pected relationships between the use of certain pesticides and prostate cancer risks. 

First, men who reported occupational use of the fumigant methyl bromide (one of 

45 common agricultural pesticides examined in the study) had a slightly higher risk 

of developing prostate cancer than the cohort overall. Second, exposure to several 

men with a family history of the disease. In addition to these novel findings, 

evidence suggests that the use of chlorinated pesticides may have been related to 

xiii 

HIGHLIGHTS OF PROGRESS

“My wife worries about all the 

chemicals I have to work 

with. 

But 

sometimes I wonder myself.” 

Genetic Polymorphism Provides Clues to Adult Brain Tumor Risk 

stood. Well established risk factors, such as high doses of radiation and certain rare 

study, investigators hypothesized that differences in the make-up of some genes 

Prostate cancer is the second leading cause of cancer death among men in the United States. Although many 

of the almost 221,000 U.S. men diagnosed with prostate cancer in 2003 will be cured, almost 29,000 will die 

from this disease in the same year. 

Researchers Uncover Possible Occupational Risk Factors of 

Prostate Cancer in Farmers 

Prostate cancer is the most common malignancy, and the second leading cause of 

cancer death, among men in the United States and in most Western countries.

A number of risk factors are implicated in the development of prostate cancer, 

including age, family history, ethnicity, hormonal factors, smoking, high 

Investigators of the Agricultural Health Study, a cohort study of over 55,000 male 

pesticide applicators with no prior history of prostate cancer, discovered two unexwidely used insecticides seemed to increase the risk of prostate cancer, but only in 

A Plan and Budget Proposal for Fiscal Year 2005 

She talks about cancer. 

I tell her not to worry. 
increased prostate cancer risk, especially in men over 50 years of age. If further 

validated, this new knowledge about the hereditary and environmental etiology of 

prostate cancer risk may help scientists develop interventions to prevent, detect, 

and treat this disease in the farming community and in other populations. 

Biobehavioral factors such as stress, depression, and social support are known to 

influence how well the immune system responds to disease, including cancers. 

Scientists have documented the effects of biobehavioral factors on the function of 

immune cells (such as white blood cells), cytokines (proteins that heighten immune 

team of investigators has extended this research to vascular endothelial growth 

factor (VEGF), a stress-related cytokine that stimulates new blood vessel growth 

were found to have a greater sense of social well being3 had markedly lower blood 

and consequent stimulation of angiogenesis, may be one way in which biobehavvalidate this mechanism and to explore ways to target it through prevention and 

treatment interventions. 

curable, with 85 percent of patients surviving at least 5 years after diagnosis. 

including leukemia, sarcoma, and breast, lung, and thyroid cancers. Among 

female survivors, breast cancer is the most likely tumor to develop, especially in 

vivors in this subgroup to identify specific risk factors. They discovered that the 

higher the radiation dose to the breast, the more likely the women were to develchemotherapy and higher radiation doses to the ovaries were associated with 

lower future breast cancer risk. Researchers suspect that premature menopause 

induced by damage to the ovaries is at the root of this risk reduction, since premature menopause by surgery is also known to reduce breast cancer risk. Because 

recently may be at lower risk for breast cancer development than the women 

will require lifetime surveillance and breast cancer prevention strategies. Despite 

the risks of future breast cancers highlighted by these investigators, the benefits 

xiv 

“When my doctor told me 

ment worked. But I’m told 

developing other cancers, 

Scary again.” 

Scientists Explore Effects of Biobehavioral Factors on Ovarian Cancer 

activity), and hormones that help regulate immune activity. For the first time, a 

(angiogenesis) in growing tumors. In this study, women with ovarian cancer who 

levels of VEGF. This research suggests that biobehavioral effects on VEGF levels, 

ioral factors affect the progression of ovarian cancer. Further research is needed to 

Breast cancer is the second leading cause of cancer death among women in the United States. Approximately 

40,000 women are expected to die from this disease in 2003. 

Investigators Study Risk Factors for Future Breast Cancers in 

Female Survivors of Hodgkin’s Disease 

Hodgkin’s disease, a once deadly cancer of the lymphatic system, is now highly 

However, with some treatments comes an increased risk of second cancers, 

women who are age 30 or younger when treated with radiotherapy. An international team of scientists recently analyzed data from over 3,800 Hodgkin’s surop breast cancer. Conversely, higher concentrations of alkylating agents given in 

of improvements to Hodgkin’s disease treatments over time, women treated more 

included in this study. However, current female survivors of Hodgkin’s disease 

The Nation’s Investment in Cancer Research 

I had cancer – Hodgkin’s 

disease – that was pretty 

scary. Thankfully, the treatI may have a greater risk of 

like breast cancer, later in life. 
the treatment-related risks. 

Pediatric Cancer Survivors 

Few would argue that cancer is a major stressor for anyone diagnosed. Recent 

research reveals that family members of cancer patients also are subject to trauma. 

Investigators applied the posttraumatic stress (PTS) model to siblings of childhood 

cancer survivors. Adolescent siblings of pediatric cancer survivors reported more 

PTS symptoms than did a reference group of unaffected teens with similar levels 

mild PTS, 32 percent indicated moderate to severe levels, and 25 percent said they 

thought their brother/sister would die during treatment. These data remind us that 

cancer is often a family disease. Consequences to siblings can include uncertainty 

about the future, distress over witnessing physical and emotional pain, sudden 

and extended separation from parents, and changes in family members’ roles and 

responsibilities. Identifying those at risk and intervening early to reduce emotional distress may be critical for the subsequent health and well being of both the 

cancer patient and his or her siblings and other family members. 

Development 

Esophageal cancer incidence has been rising at a rate faster than that of any other 

in the advanced stages of disease, and mortality is high. Investigators recently discovered that an artificial intelligence technique called “artificial neural networks” 

gence techniques for distinguishing between esophageal cancer and a precancerous 

recognize the difference between biopsy samples from patients with BE or 

thus “learned” the difference in what the microarray data of cancer and precancer 

“looks” like. Once fully trained, the ANNs correctly classified 10 new samples as 

management. Furthermore, the ANN-identified differences in gene expression 

xv 

HIGHLIGHTS OF PROGRESS

4 

, 

esophagus. No big deal 

right? Most people with 

be me, right? 

of radiotherapy and chemotherapy for Hodgkin’s disease patients far outweigh 

Effects of Stress Can Linger for Family Members of 

of general anxiety. Among the survivors’ siblings, about half (47 percent) reported 

Some cancers can be treated successfully if detected early. Unfortunately, for many, like esophageal cancer, 

we do not have good early detection tests. Researchers are using genomics and proteomics to develop tests 

to screen for hard-to-detect cancers. 

Researchers Use Artificial Neural Networks to Study Esophageal Cancer 

malignancy. With no good test for early detection, patients are usually diagnosed 

(ANNs) can accurately analyze microarray data to detect esophageal cancer. 

In this study, investigators identified ANNs as the best of several artificial intellicondition, Barrett’s esophagus (BE). Investigators first “trained” the ANNs to 

esophageal cancer. To train the ANNs, researchers had it analyze eight tissue samples from BE patients and four from patients with esophageal cancer. The ANNs 

BE or esophageal cancer. This research shows ANNs as a promising technique 

that can extract and analyze microarray data. With further development, this 

technology may have a far-ranging impact on cancer detection, diagnosis, and 

A Plan and Budget Proposal for Fiscal Year 2005 

“Okay, I knew I had GERD

and now I have Barrett’s 

Barrett’s esophagus don’t 

get cancer, right? So it won’t 

No problem. 

Still, I wonder if there’s a 

good way to screen for this 

cancer, just to be safe.” 
discovered in this study may provide biomarkers that can be used to develop early 

detection techniques for esophageal cancer. 

Screening for Genetic Mutation May Improve Detection and 

Treatment of Thyroid Cancer 

Papillary thyroid cancer is the most common and most curable type of thyroid 

cancer, with approximately 95 percent of patients cured if treated appropriately. 

However, scientists believe survival rates could be further improved if clinicians 

had better tools for early detection. Tumors are usually detected after a patient or 

family member notices a lump in the neck, and a physician recommends a clinical needle biopsy. However, these needle biopsies are often not definitive, and 

patients undergo unnecessary surgery or delayed diagnosis. Scientists have now 

discovered a genetic mutation that may assist physicians in identifying tumors 

earlier. In a recent study, investigators screened tumor tissue from six different 

disease sites for a cancer-related genetic mutation prevalent in melanoma cancers. 

This mutation of the BRAF gene was detected in 24 of 35 tumors of the papillary 

thyroid (69 percent). In addition to providing a potential aid for early detection, 

this discovery provides clues about the molecular pathways that may be involved 

in the development and progression of this cancer. Further research into these 

molecular mechanisms may lead to new treatments for people who do not 

respond to current therapies. 

Osteopontin Gene May Aid Detection and Treatment of 

Metastatic Liver Cancer 

Hepatocellular carcinoma (HCC or liver cancer) is an extremely aggressive disease of high mortality that is common in Asia and Africa, with incidence rising in 

Europe and North America. Metastasis within the liver causes most of the mortality from this disease. Researchers used gene expression microarrays to identify 

genes that affect both tumor metastasis and patient survival for HCC. These 

investigators identified, for the first time, a molecular signature to distinguish 

between metastatic and nonmetastatic hepatocellular cancers. Of special note, 

the gene osteopontin was overexpressed in metastatic HCC compared to nonmetastatic tumors. Correlative laboratory experiments were encouraging. 

Investigators were able to block the metastatic behavior of HCC cells in vitro 

with an antibody that inhibits the action of the osteopontin protein. The same 

antibody prevented HCC metastasis to the lungs in a mouse model. Further 

research is needed to refine and validate the clinical usefulness of this promising 

biomarker. If developed for early detection of metastatic HCC and for therapy to 

prevent metastasis, this discovery could improve long-term survival of patients 

who ordinarily succumb to this disease. 

xvi The Nation’s Investment in Cancer Research 
prostate cancer are usually given the choice of treatment by radical prostatectowith lymph node metastasis is a more aggressive treatment with adjuvant androgland must be surgically removed and examined in the laboratory for metastasis. 

No imaging technique has proven sufficiently sensitive to replace this invasive 

lymphotropic superparamagnetic nanoparticles (LSNs) to enhance imaging of 

lymph nodes in prostate cancer patients. LSNs, small enough to enter individual 

cells, actively accumulate in lymph nodes once injected into the body and are sufficiently magnetic to be detected by magnetic resonance imaging (MRI). Animal 

studies have shown that MRI using LSNs can distinguish between normal and 

metastatic lymph nodes. Investigators have used LSNs in conjunction with MRI 

to correctly identify lymph node metastasis in 100 percent of 33 patients known 

determine the clinical utility of this promising new procedure. 

Lung cancer is the leading cause of cancer death in both men and women in the United States. Close to 92,000 

Investigators studying non-small cell lung cancer (NSCLC) recently built on 

findings that a vaccine containing genetically modified irradiated tumor cells is 

highly active against tumors in a number of mouse models as well as in some 

melanoma patients. In a Phase I clinical trial, researchers produced patientspecific vaccines by isolating, genetically modifying, and irradiating tumor cells 

taken from patients with metastatic NSCLC. The genetic modification caused the 

cells to produce granulocyte macrophage colony-stimulating factor (GM CSF), a 

protein known to activate the immune system to attack tumor cells. The radiation rendered the tumor cells unable to replicate. The vaccine caused only 

low-level toxicities, and 18 out of 25 vaccinated patients showed at least some 

immune response. The disease of five patients was stabilized for up to 3 years 

after treatment. Of patients whose tumors were surgically removed before vaccination, two were still cancer free 31

/2 

uniform across all patients, this study adds to accumulating evidence that GM 

CSF-based vaccines activate the immune system to attack tumors in many cancers 

and could perhaps be combined effectively with other treatment strategies. The 

prolonged response of some patients suggests promise for this vaccine strategy in 

early-stage NSCLC patients. 

xvii 

HIGHLIGHTS OF PROGRESS

“How am I going to tell my 

family about my lung cancer 

diagnosis? The doctor says 

it might buy me some extra 

doctor did tell me about a 

New Type of Nanoparticle Improves Imaging of Lymph Nodes in 

Prostate Cancer Patients 

Testing for the presence or absence of lymph node metastasis is an important 

element in the care of men diagnosed with prostate cancer. Men with local 

my, radiotherapy, or watchful waiting. However, the standard of care for men 

gen-deprivation therapy with radiation. Currently, lymph nodes near the prostate 

biopsy procedure. But recently, researchers tested a type of nanoparticle called 

to have metastatic prostate cancer. This test also correctly classified 96 percent of 

patients with nonmetastatic cancer. Large prospective clinical trials are needed to 

men and 80,000 women will be diagnosed with lung cancer in 2003. In the same year, the disease will kill over 

88,000 men and close to 69,000 women. Non-small cell lung cancer is the most common form of lung cancer. 

Cancer Vaccine Shows Promise for Non-Small Cell Lung Cancer 

years later. While the response was not 

A Plan and Budget Proposal for Fiscal Year 2005 

standard treatments don’t 

cure many patients with this 

type of lung cancer, although 

time. Time is precious. The 

clinical trial. But I don’t know. 

Is there really hope?” 
Researchers Identify Prognostic Factors for Survival in 

Pancreatic Surgery Patients 

Pancreatic cancer is a high-mortality disease with an overall 5-year survival rate 

for patients with adenocarcinoma, the most common form of this disease, at less 

than 5 percent. Only about 10 percent of adenocarcinoma patients are diagnosed 

while the cancer is confined to the pancreas. These patients are eligible for surgical resection, and their 5-year survival rate increases to about 20 percent. 

Recently, a team of investigators accessed data from NCI’s Medicare-linked 

Surveillance, Epidemiology, and End Results (SEER) registries to examine the 

prognostic factors that influence survival in this group of patients. This retrospective cohort analysis of 396 adenocarcinoma surgical patients revealed that 

the strongest predictor of improved survival was postoperative adjuvant 

chemoradiation therapy. The investigators also found that a trend toward more 

patients being treated in teaching hospitals was leading to a gradual improvement 

in survival over time. Other predictors of improved survival included tumor size 

of less than 2 centimeters in diameter, no detection of cancer in nearby lymph 

nodes, well-differentiated histology, and high socioeconomic status. African 

Americans tended to have lower overall survival rates than other racial/ethnic 

groups. Of special note, socioeconomic status was shown to affect the likelihood 

of receiving adjuvant treatment, the most powerful predictor of survival. 

Delivery	 The Steroid Dexamethasone Improves Survival of Children with 

Acute Lymphoblastic Leukemia 

Survival outcomes for children with acute lymphoblastic leukemia (ALL) have 

improved dramatically over the years. The number of young patients who survive 

5 or more years has risen from less than 5 percent in the early 1960s to more 

recent rates of about 85 percent. This improvement is a testament to the success 

of sequential clinical trials that have progressively identified more effective treatment regimens. Recent conventional therapy for childhood ALL has included 

chemotherapy with mercaptopurine, accompanied by treatment with the steroid 

prednisone to help kill the cancer cells. Researchers have now discovered that 

replacing prednisone with a different steroid, dexamethasone, further improves 

survival. In a clinical trial of more than 1,000 standard-risk ALL patients younger 

than 10 years of age, 85 percent of those given dexamethasone survived at least 

6 years without evidence of relapse, versus 77 percent of patients treated with 

prednisone. Fewer children treated with dexamethasone experienced central 

nervous system relapses, an important cause of treatment failure for children 

with ALL. There was also a trend toward fewer ALL relapses in bone marrow. 

These findings change the standard of treatment for ALL patients younger than 

10 years of age by making dexamethasone, rather than prednisone, the steroid of 

choice. Additional research is needed to evaluate the use of dexamethasone in the 

treatment of older children and adolescents with ALL. 

xviii The Nation’s Investment in Cancer Research 
GleevecTM May Be Used to Treat Rare Cancer 

Idiopathic Hypereosinophilic Syndrome 

Idiopathic hypereosinophilic syndrome (IHS) is a condition in which the body 

produces an overabundance of eosinophils, a type of white blood cell involved in 

ridding the body of foreign substances. The cause of this anomaly is unknown. 

Current treatments focus on controlling deadly damage to vital organs that 

become infiltrated by eosinophils, but mortality nevertheless is extremely high. 

Researchers recently treated 11 IHS patients with an experimental trial of 

Gleevec, a molecularly targeted drug used to treat chronic myelogenous leukemia 

(CML) and gastrointestinal stromal tumors (GIST). In 9 of 11 patients, eosinophil 

levels returned to normal, in treatment responses lasting three or more months. 

Based on knowledge of Gleevec’s mechanism of action, investigators searched for 

and identified the genetic mutation causing IHS in the majority of these patients. 

In addition to survival benefits for IHS patients, this work sheds light on the 

molecular origins of IHS, which may lead to a better understanding of this disease and still better ways to treat it. This study also points to a perhaps even 

greater number of cancers that may respond to Gleevec and encourages continued searching for molecular targets for this drug in a variety of disease sites. 

Improved Therapy Boosts Survival of AIDS-Related Lymphoma Patients 

Survival of HIV-positive patients with AIDS-related lymphoma (ARL) has 

improved since treatment with highly active antiretroviral therapy (HAART) for 

AIDS patients has become standard practice. However, prognosis remains poor 

with the standard treatment for ARL, the CHOP5 regimen — ARL still causes 

death in up to 20 percent of HIV-positive patients. Researchers recently developed 

a treatment regimen known as dose-adjusted EPOCH6 (DA-EPOCH) that substantially improves survival for ARL patients. Three factors make DA-EPOCH 

effective in these patients. First, given in low concentrations over long periods, this 

drug combination can overcome the drug resistance encountered with CHOP therapy. Second, the patients receive individualized dosages to minimize certain toxicities. And third, antiretroviral therapy can safely be suspended during chemotherapy to boost the effectiveness of the treatment. Out of 39 patients treated with DAEPOCH, 29 experienced complete remission, and 5 achieved partial remission. 

Over the long term, 60 percent of the patients survived at least 53 months; 92 percent of these were disease free. These survival rates are dramatically better than for 

patients given standard CHOP therapy. Researchers expect DA-EPOCH therapy 

to greatly boost survival of ARL patients, with the exception of those with central 

nervous system involvement who did not respond well to DA-EPOCH therapy. 

A Plan and Budget Proposal for Fiscal Year 2005 xix 

HIGHLIGHTS OF PROGRESS 
Although close to 61 percent of new cancer cases occur among persons 65 years 

population, only 25 percent of the patients enrolled in cancer clinical trials are 

from this age group. NCI-supported researchers examined the reasons behind this 

disparity by conducting a retrospective analysis of patient and trial characteristics 

for 59,300 patients enrolled in 495 NCI-supported trials. Of all the criteria used 

for excluding participation in a trial, exclusions based on organ system abnormalities and functional status limitations were found to be most significant for low 

participation by older patients. Overall, older patients do have more disqualifying 

medical conditions than younger patients. Investigators noted that while insurance 

coverage for clinical trials for the aging has improved access to trials for this population group, changes in study design and in protocol exclusions are needed to 

improve overall enrollment opportunities. Results from this study suggest that if 

protocol exclusions were relaxed, participation by this age group in cancer trials 

could be as high as 60 percent. The investigators emphasized that clinical trials 

must have exclusion criteria. For example, normal renal function may be required 

tors suggest that, when designing a clinical trial, researchers must examine each 

exclusion criterion to ensure it is scientifically justified. 

are better when patients are treated at hospitals that perform a large number of 

the surgeries (“high-volume” hospitals). A recent study of over 7,000 rectal 

cancer patients has revealed that rates for permanent colostomy and postoperative mortality were lower and overall survival higher for rectal cancer patients 

undergoing surgery at high- compared to low-volume hospitals. It is particularly 

important to understand the relationship between hospital volume and patient 

this disease to markedly affect tumor control and quality of life. This research 

suggests that the morbidity and mortality of rectal cancer could be substantially 

reduced if all patients were to receive the same quality of care found at highvolume hospitals. Researchers recommend additional investigation to identify 

processes of care that contribute to these differences in patient outcomes. Many 

factors, including but not limited to quality of imaging, anesthesia support, 

surgical technique, and nursing care could be examined. Such information would 

help scientists to design clinically meaningful approaches to assessing and 

xx 

I have to tell my patients they 

the easier cases. With quality 

he has a good chance of full 

Participation of Older Patients in Cancer Clinical Trials Could Be 

Improved by As Much As 60 Percent 

of age and older, and approximately 71 percent of all cancer deaths are in this 

in trials that use agents that can cause kidney toxicity. However, these investigaIncidence and mortality rates for cancers of the colon and rectum are the third highest in the United States for 

both men and women. Statisticians predict that in 2003, more than 144,000 people will be diagnosed with, and 

more than 57,000 will die from, colorectal cancer. 

Rectal Cancer Patients Fare Better at Hospitals with High Surgical Volume 

For many cancers requiring surgery, patient survival and quality-of-life outcomes 

outcomes for rectal cancer, because scientists have found surgical management of 

improving quality of care for all patients with rectal cancer. 

The Nation’s Investment in Cancer Research 

“As a doctor, it isn’t easy when 

have cancer. This was one of 

surgical care and adjuvant 

therapy for his rectal cancer, 

recovery.” 
prospective cohort study of postmenopausal U.S. women age 50 to 79, demonstrate a protective role for physical activity on breast cancer risk. Risk reductions 

were higher in healthy weight than overweight women, with decreasing benefit 

earlier ages had the greatest reductions in risk with current physical activity also 

protective. Investigators noted the lowest risk levels in women who were the most 

physically active, although even moderate activity was protective. This finding 

may be especially encouraging to older women who may be able to achieve moderate, but not strenuous, exercise levels. For example, breast cancer risks were 

18 percent lower in women who walked briskly for a total of 1-1/2 to 2-1/2 hours 

weekly than in inactive women. The walking did not have to be done all at once, 

but could be spaced throughout the week. Another promising finding is that 

physical activity reduced risk among women on hormone replacement therapy 

menopausal symptoms. 

. 

1 Prepared by the National Cancer Institute, the Centers for Disease Control and Prevention, the National Center for Health 

2 

3 

malignant disease, and the Profile of Mood States. 

4 

5 Cyclophosphamide, doxorubicin, vincristine, and prednisone. 

6 Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. 

xxi 

HIGHLIGHTS OF PROGRESS 

“I eat my fruits and vegetamuch. 

seemed to be something else 

that needed doing. I just 

never got to it. 

says walking just a half hour 

a day would help.” 

Abundant evidence now links diet, physical activity, and weight to cancer risk, development, and progression. 

NCI and partners support programs such as 5 A Day for Better Health and Men: Shoot for 9 for Better Health 

to deliver the message of cancer prevention through more healthful lifestyle choices. With increasing evidence 

of the role that lifestyle factors can play in reducing the cancer burden, NCI has begun placing even greater 

emphasis on this area of research. (See pages 45-50.) 

Recreational Activity Reduces Breast Cancer Risk in 

Postmenopausal Women 

Data from the Women’s Health Initiative (WHI) Observational Study, a large 

with increasing obesity. Women who reported engaging in strenuous activity at 

(HRT). Since HRT is known to slightly increase breast cancer risk, physical activity may provide a countermeasure for women who wish to continue HRT for 

The quotes in this chapter are representative of many people’s experiences with cancer

Statistics, the American Cancer Society, and the North American Association of Cancer Registries. seer.cancer.gov/reportcard 

Other than nonmelanoma skin cancer. 

According to two measures: the Functional Assessment of Cancer Therapy, which measures quality of life in patients with 

GERD, gastroesophageal reflux disease, is a risk factor for Barrett’s esophagus, where cells lining the lower part of 

the esophagus are replaced by cells resembling the lining of the stomach. Barrett’s esophagus is a risk factor for 

esophageal cancer. 

A Plan and Budget Proposal for Fiscal Year 2005 

bles, but I’ve never exercised 

It’s so hard to get 

started, and there always 

I figured I was 

too old for it to make a difference now, but my doctor 
Other Highlights in This Document


Discovery 

Development 

Delivery 

Genetics of programmed cell death, page 17 

Genetic subtypes of breast cancer, page 18 

Imaging molecular interactions in cells, page 32 

Genetics of smoking cessation, page 39 

Imaging nicotine receptors in the brain, page 39 

ADHD and tobacco marketing, page 39 

Discoveries in energy balance research, pages 46 and 47 

Assessing quality of cancer care, page 52 

Genetics of neuro-cognitive late effects, page 67 

Ovarian cancer screening test, page 17 

Genetic prognosis of ovarian cancer tumors, page 18 

Recent research on cancer and viruses, page 19 

Immune therapy for metastatic melanoma, page 26 

Prostate cancer and diet, page 27 

Improving cervical cancer screening, page 74 

Classifying diffuse large B-cell lymphoma subtypes, page 84 

Chemoprevention of prostate cancer, page 92 

Improved survival for Ewing’s sarcoma patients, page 8 

Celecoxib and cancer prevention, pages 23 and 87 

Nicotine, dopamine metabolism, and tobacco cessation, page 39 

Assessing dietary intake measures for clinical trials, page 45 

Recent patterns of care studies, page 53 

Recent childhood survivorship research, page 69 

AvastinTM and renal cell and colorectal cancer treatment, pages 84 and 87 

VelcadeTM, proteasomes, and multiple myeloma treatment, pages 85 and 89 

Improved survival for breast cancer patients, page 89 

Improved survival for endometrial cancer patients, page 89 

Aspirin and colorectal cancer prevention, page 92 

Tamoxifen and benign breast disease prevention, page 92 

xxii The Nation’s Investment in Cancer Research 
The Challenge Is Before Us and the Opportunity Is Now. 

Our Action Plan for Fiscal Year 2005 

In 2001, the National Cancer Institute (NCI) issued to the nationwide cancer community a Challenge Goal: 

Eliminate the suffering and death due to cancer by 2015. 

Never before have so many scientific tools and technologies and so much biomedical 

knowledge been assembled to power our ability to reach our Challenge Goal. The 

cancer community is currently experiencing exponential growth in its knowledge of 

cancer as a disease process, growth that has been fueled by historically high levels of 

funding, scientific expertise, infrastructure, and enabling technologies. With a sharp 

focus on our goal and continued budgetary support, we will be able to assemble the 

necessary pieces and achieve the type of progress needed to remove the ring of fear 

from the word “cancer” for future generations. 

NCI will concentrate its research investments on preempting the process of cancer by 

preventing its initiation; detecting it early; and slowing, stopping, or reversing the 

cancer process so that it cannot progress to a lethal phenotype. We will also work to 

ensure that emerging knowledge is used immediately to develop, test, and deliver 

new interventions for public health programs, medical practice, and policy making. 

Our success will depend on our ability to seamlessly integrate activities both within 

NCI and with our partners, remove major barriers to progress, and ensure that all 

new activities are informed by lessons learned along the way. 

DISCOVERY, DEVELOPMENT, AND DELIVERY AS A SEAMLESS PROCESS 

As the leader of the National Cancer Program, NCI provides vision and leadership 

to the nationwide community of researchers, public health workers, healthcare 

providers, patients, advocates, and policy makers working to defeat cancer. We 

strive to facilitate a seamless process for integrating discovery activities, accelerating 

the development of new interventions, and ensuring the delivery of new evidencebased interventions for all cancers and all people in need. We must ensure that results 

of research are continuously evaluated for their potential for practical application 

and quickly moved into arenas of developmental research. Throughout all of our 

efforts in discovery and development, we must have an eye toward the delivery of 

validated interventions to clinical practice and public health settings. Likewise, as 

interventions are taken to the people, we must continue to study their impact on 

individual and public health to inform future research and development. Movement 

in each of our priority areas along the discovery-development-delivery research continuum must be smooth and unencumbered by traditional infrastructure boundaries 

and linear ways of thinking. 

A Plan and Budget Proposal for Fiscal Year 2005 1 
outlines our next steps in achieving our Challenge Goal to eliminate 

existing and new knowledge for the development and application of evidence-based interventions, all of which 

• The genetic, environmental, and lifestyle factors and their interactions that 

define cancer risk. 

• The interaction between cancer cells and their microenvironment. 

• 

ronmental factors to influence the cancer process. 

• The causes of tobacco use, addiction, and tobacco-related cancers. 

• The biological, physical, psychological, and social mechanisms, and their inter­

• The scientific basis for quality cancer care. 

• The fundamental causes of cancer health disparities. 

• Imaging methods, molecular biosensors, and imaging-guided interventions. 

• Molecular targets for treatment and prevention. 

interventions including: 

• Strategies to address the clinical, behavioral, and societal issues associated 

• 

• New drugs and reagents that target cells in the microenvironment. 

• Novel combinations of drugs and modalities that can preempt or arrest 

• Imaging and molecular biosensors for use in early detection, diagnosis, 

treatment, and prediction. 

• New approaches to the prevention and treatment of tobacco use, nicotine 

addiction, and tobacco-related cancers. 

• 

• Process and outcome measures for assessing the quality of cancer care. 

• Incorporation of symptom management and palliative care into quality care 

improvement. 

• 

• 

2 

Discovery 

Objectives 

Development 

Objectives 

NCI’s Action Plan for Fiscal Year 2005 

the suffering and death due to cancer. It includes continued work in broad research areas and optimal use of 

will have implications for many types of cancer. 

To advance toward our goal to eliminate the suffering and death due to cancer, 

we must continue to improve our understanding of: 

How body weight, physical activity, and diet interact with genetic and enviactions that affect a cancer patient’s response to disease, treatment, and recovery. 

. . . then use that information to develop highly effective evidence-based 

with cancer susceptibility. 

Validated molecularly targeted drugs for treatment and prevention. 

malignancy. 

Tools to improve physical fitness, diet, and weight control. 

Specific approaches to reducing cancer-related health disparities. 

Strategies for reducing cancer-related chronic or late morbidity and mortality. 

The Nation’s Investment in Cancer Research 
• Make novel and effective prevention, early detection, and prediction 

measures available to all who need them. 

• Deliver targeted and effective therapeutic interventions to all cancer 

patients. 

• 

and sedentary lifestyle. 

• 

quality cancer care. 

• Eliminate the adverse effects of cancer diagnosis and treatment on 

cancer survivors. 

• Capture the experience and knowledge gained from application to 

the behavioral sciences. 

Delivery 

Objectives 

. . . and ensure that these new interventions are used to: 

Eliminate cancer-causing behaviors such as tobacco use, unhealthy diet, 

Eliminate disparities in cancer incidence, mortality, and access to 

inform future discovery in cancer biology, molecular epidemiology, and 

To meet these objectives for research discovery, development, and delivery, we must optimize our 

research platforms and enable investigators to work at peak efficiency. Our success in achieving these 

objectives will depend on our ability to: 

Platforms • Accelerate innovation in investigator-initiated research by expanding


for Discovery, access to resources and new technologies.


Development, and • Integrate infrastructures and collaborations through Cancer Centers, 


Delivery networks, and consortia to address large problems in human cancer. 


•	 Ensure that our national clinical trials program addresses the most important research questions quickly and effectively. 

•	 Promote networks, partnerships, and coalitions to translate results of 

research into clinical practice and public health benefit. 

Enablers •	 Create and use bioinformatics and analytical tools to redefine how cancer

of Discovery, research is conducted; care is provided; and patients, physicians, and


Development, and researchers interact.


Delivery • Understand, apply, and disseminate communication approaches that 


maximize access to and appropriate use of cancer information by all who 

need it. 

A Plan and Budget Proposal for Fiscal Year 2005 3 
Toward Our Challenge Goal: 


Budget Increase Request for Fiscal Year 2005


Broad Research Priorities (dollars in thousands) 

Core Scientific Areas 

We will be able to accelerate our understanding of the causes of cancer through 

large-scale studies in Genes and the Environment. $73,150 

We will further explain the biological mechanisms that influence the development and progression 

of cancer through studies on the Signatures of the Cancer Cell and Its Microenvironment. $35,300 

As we more fully understand the causes, development, and progression of cancer, we will be 

able to accelerate the validation of Molecular Targets of Prevention, Diagnosis, and Treatment. $47,650 

And we will continue to expand the discovery and development of Imaging tools, accelerate the 

development of image-guided interventions, and stimulate research on in vivo Molecular Sensing. $44,750 

Areas of Public Health Emphasis 

We will continue to investigate the pervasiveness and causes of Tobacco Use and 

Tobacco-Related Cancers and apply this knowledge to prevention and treatment. $75,000 

Studies in Optimizing Energy Balance will help us better understand the interactions among 

weight, physical activity, diet, and cancer and apply this knowledge to cancer prevention 

and control. $57,800 

We will strengthen the scientific basis for public and private decision making to Improve the 

Quality of Cancer Care on behalf of millions of people who do not receive adequate cancer care. $36,300 

We will work to Reduce Cancer-Related Health Disparities for the untold numbers of 

people who suffer because of social or economic status, cultural or language barriers, or 

geographic location. $71,300 

We will work to better understand Cancer Survivorship and develop interventions that will 

optimize health and quality of life after cancer. $30,250 

Platforms for Discovery, Development, and Delivery 

Investigator-Initiated Research builds on the synergism at institutions across the country to 


ask the critical questions, explore research options, and develop and test innovative technologies. $123,501 


Centers, Networks, and Consortia allow investigators to work in teams, collaborate for progress, 


and ensure that results advance from discovery to intervention development and delivery. $96,800 


NCI’s National Clinical Trials Program provides the infrastructure to move new cancer 


interventions from the laboratory to studies in people and then to the healthcare setting. $334,900 


Enablers of Discovery, Development, and Delivery 

We will harness Bioinformatics tools to integrate data, capture and share research outcomes, 


and provide tools for patients to interact more directly with cancer researchers. $40,800 


As we better understand, apply, and disseminate effective Communication approaches, we will 


be able to maximize access to and appropriate use of cancer information by all who need it. $43,500 


Total Increase Request for Fiscal Year 2005 Priority Areas $1,111,001 

A Plan and Budget Proposal for Fiscal Year 2005 
The Nation’s Investment in Cancer Research


Distribution of 2005 Budget Request ($6,211,000,000) 

Cancer Centers 6.8% 

SPOREs 3.8% 

Other Grants 1.5% 

Research Project Grants 46.1% 

Intramural Research 12.3% 

Clinical Trials Infrastructure 8.1% 

Training and Education Grants 3.2% 

Cancer Control Operations 3.1% 

Research Support Contracts 11.7% Research Management and Support 3.3% 

Distribution of 2005 Requested Increases ($1,440,481,000) 

Cancer Centers 8.3% 

SPOREs 4.5% 

Other Grants 1.9% 

Research Project Grants 43.5% 

Intramural Research 4.1% 

Clinical Trials Infrastructure 15.7% 

Training and Education Grants 0.9% 

Cancer Control Operations 1.5% 

Research Support Contracts 16.9% Research Management and Support 2.6% 

Research Project Grants 

Funding for extramural research, primarily 

through investigator-initiated Research 

Project Grants (RPGs), comprises the largest 

part of the NCI core budget. Increases 

through the NCI Challenge and Extraordinary 

Opportunity initiatives contribute to the 

expansion of research supported through 

RPGs. NCI funds about 4,800 RPGs each 

year to nearly 600 institutions across the 

United States at an average cost of approximately $400,000 per grant. If fully supported, our budget request for Fiscal Year 2005 

would add $594 million to the funds available 

to support investigator-initiated research. 

Intramural Research 

NCI intramural research focuses on projects 

conducted by some 400 researchers located 

on the NIH campus. These researchers build 

upon the proximity between their research 

laboratories and the NIH Clinical Center and 

the synergism among NIH Institutes to support the rapid translation of basic laboratory 

research to the clinic and to maintain a 

special focus on long-term epidemiologic and 

genetics studies. 

Cancer Centers and Special Programs of 

Research Excellence (SPOREs) 

Sixty NCI-supported Cancer Centers serve as 

hubs for cutting-edge research, high quality 

cancer care, and outreach and education for 

healthcare providers and patients. Centers of 

Excellence like the SPOREs use flexible funding to pursue questions related to specific 

forms of cancer and to move disease-specific 

research quickly from the laboratory to the 

patient. Funding increases will allow NCI to 

broaden the number and range of activities at 

Cancer Centers and SPOREs. 

The Nation’s Investment in Cancer Research 
National Cancer Institute 

Budget Request for Fiscal Year 2005 

2003 

Operating 

(dollars in thousands) Budget 

2004 2005 Budget Request 

President’s 

Budget Increases Total 

Research Project Grants (RPGs) 

Ongoing 

New and Renewal 

Small Business Innovation Research 

(SBIR) 

Intramural Research 

Cancer Centers 

Specialized Programs of Research 

Excellence (SPOREs) 

Clinical Trials Infrastructure 

Cooperative Clinical Research 

Community Clinical Oncology Program 

Subtotal RPGs 

Total RPGs 

(CCOPs) 

$1,588,852 

491,556 

2,080,408 

90,554 

2,170,962 

648,227 

267,430 

163,403 

156,582 

95,905 

$1,614,169 

523,295 

2,137,464 

101,210 

2,238,674 

704,551 

302,281 

170,700 

180,330 

95,458 

$122,985 

471,429 

594,414 

32,566 

626,980 

59,000 

120,225 

65,383 

149,851 

76,200 

$1,737,154 

994,724 

2,731,878 

133,776 

2,865,654 

763,551 

422,506 

236,083 

330,181 

171,658 

Subtotal Clinical 

Training and Education Grants 

National Research Service Awards 

Research Career Program 

Cancer Education Program 

Minority Biomedical Research Support 

Subtotal Training an

Cancer Control Operations 

Research Support Contracts 

Research Management and Support 

Other Grants 

Tota

Cancer Control included above** 

Trials Infrastructure 

d Education Grants

l Budget Request 

252,487 

66,570 

69,063 

30,849 

8,385 

174,867 

172,021 

515,190 

166,483 

61,278 

$4,592,348 

555,863 

275,788 

75,048 

66,827 

32,206 

11,372 

185,453 

174,355 

485,790 

170,208 

62,719 

$4,770,519 

554,290 

226,051 

3,477 

4,205 

4,563 

375 

12,620 

21,204 

243,131 

37,817 

28,070 

$1,440,481 

285,087 

501,839 

78,525 

71,032 

36,769 

11,747 

198,073 

195,559 

728,921 

208,025 

90,789 

$6,211,000 

839,377 

Clinical Trials Infrastructure 

NCI supports clinical trials at the NIH clinical 

center and close to 3,000 other sites across 

the U.S. each year. Over 1,500 trials are conducted annually, involving more than 12,000 

investigators assisting thousands of patients. 

These trials make possible the testing of 

targeted agents that hold promise for more 

effective, less invasive, cancer prevention and 

treatment and technologies that can be used 

for better detection and diagnosis. About 

three-quarters of this funding is for treatment 

trials and the other quarter supports prevention and screening trials. 

Training and Education Grants 

NCI funds approximately 200 institutions 

and 2,200 individuals each year through 

extramural cancer research training programs 

to prepare the next generation of scientists 

and clinicians to use new technologies and 

work effectively in interdisciplinary, collaborative research environments. Increased funding 

will be used to enhance these programs and 

to support the participation and growth of 

scientists within underserved populations. 

Cancer Control** 

NCI’s cancer control operational funds along 

with numerous grants and contracts included 

throughout the budget are used to support 

research, communication, and other activities 

focused on ways to reduce cancer risk, incidence, morbidity, and mortality and improve 

the quality of life for all cancer patients. 

Increases will be used to support research on 

tobacco and tobacco-related cancers, reducing 

cancer-related health disparities, improving 

the quality of cancer care, cancer survivorship, 

cancer communications, and a host of other 

information dissemination activities. 

4 The Nation’s Investment in Cancer Research 
Requested Increases for Fiscal Year 2005 

Platforms for Enablers for


Broad Discovery, Discovery,


Research Development, Development, 


(dollars in thousands) Core Priorities and Delivery and Delivery Total 

Research Project Grants (RPGs) 

Ongoing $122,985 $122,985 

New and Renewal 62,378 $260,500 $131,551 $17,000 471,429 

Subtotal RPGs 185,363 260,500 131,551 17,000 594,414 

Small Business Innovation 

Research (SBIR) 22,566 8,000 - 2,000 32,566 

Total RPGs 207,929 

Intramural Research 33,250 

Cancer Centers 9,975 

Specialized Programs of Research 

Excellence (SPOREs) 5,633 

Clinical Trials Infrastructure 

Cooperative Clinical Research 5,951 

Community Clinical Oncology Program 

(CCOPs) 3,150 

268,500 

15,500 

13,250 

40,750 

9,000 

1,500 

131,551 

9,500 

96,000 

18,000 

134,900 

71,550 

19,000 

750 

1,000 

1,000 

-

-

626,980 

59,000 

120,225 

65,383 

149,851 

76,200 

Subtotal 9,101 10,500 206,450 - 226,051 

Clinical Trials 

Infrastructure 

Training and Education Grants 

National Research Service Awards 2,477 1,000 - - 3,477 

Research Career Program 2,205 2,000 - - 4,205 

Cancer Education Program 1,063 3,500 - - 4,563 

Minority Biomedical Research Support 375 - - - 375 

Subtotal 6,120 6,500 - - 12,620 

Training and 

Education Grants 

Cancer Control Operations 13,754 2,450 5,000 - 21,204 

Research Support Contracts 16,031 99,800 69,550 57,750 243,131 

Research Management and Support 5,617 9,250 18,150 4,800 37,817 

Other Grants 22,070 5,000 1,000 - 28,070 

Total Increase $329,480 $471,500 $555,201 $84,300 $1,440,481 

Request 

Research Support Contracts 

Research support contracts are used to support program efforts across the Institute. 

Areas that utilize contracts are diverse and 

include such areas as drug development, cancer control research, information dissemination, and support to epidemiological research. 

Research Management and Support 

Research management and support budgets 

are used for the critical technical and administrative services required for NCI to carry out 

its work. They include central administrative 

functions, overall program direction, grant 

and contract review and administration, personnel, program coordination, and financial 

management. 

Other Grants 

Other grants support partnerships and 

shared resources and scientific evaluation, 

workshops, and conferences. 

A Plan and Budget Proposal for Fiscal Year 2005 5 
6 The Nation’s Investment in Cancer Research

Disease-Specific Research: Advancing National Agendas

Unlike the commonly held belief of 30 or 40 years ago, we know today that there are more than 100 distinct

types of cancer. We are also learning that several of these have subtypes with unique molecular characteristics that influence how they develop and progress and how they can be effectively prevented, detected, and

treated. While the majority of the research supported by NCI has broad application across various types of

cancer, we also have in place plans for ensuring coverage of essential research directed toward specific types

of cancer. This disease-specific focus is absolutely critical to achieving our Challenge Goal and is bolstered

by recent gains in understanding the molecular features both shared by and unique to specific cancers.

Ultimately, we look for ways to apply all of our research results to the development and delivery of diseasespecific interventions. 

NCI’s Planning and Evaluation Process for 

Disease-Specific Research 

NCI’s planning and evaluation process for disease-specific research

involves three distinct phases: (1) developing recommendations

through external Progress Review Groups (PRGs), (2) planning for

and implementing initiatives that respond to these recommendations

with advice from internal implementation working groups, and (3)

reporting on progress. This comprehensive and integrated approach

to planning and evaluation helps us demonstrate progress toward our

Challenge Goal and the wise use of resources to the scientific community and the public. Through these and other crosscutting efforts,

NCI has established a framework for accountability that is consistent with the

President’s Management Agenda (PMA) and the congressionally mandated

Government Performance and Results Act (GPRA). 

During the past seven years, NCI has called upon a number of PRGs, each composed

of prominent members of the scientific, clinical, industry, and advocacy communities, to assess the state of the science and recommend future research-related 

priorities for specific types or groups of related cancers. Go to prg.nci.nih.gov for

additional information about and reports from each of these PRGs.

Impacts of PRGs on Disease-Specific Research Agendas

PRG recommendations are central to sustaining the best possible science and 

making the fastest advances against specific cancers and have proven to be a valuable asset to NCI strategic planning. For example:

• PRGs have helped shape research directions. PRG reports have had substantial

impact. NCI divisions and programs use them in planning and developing new initiatives. Extramural scientists cite them in their grant applications. They are cited 

regularly in Congressional documents. And they are used by advocates, researchers,

and members of professional societies to attract funding from other sources. 

• PRGs have led to an expanded understanding and awareness of opportunities

related to cancer research. PRG members and roundtable participants report

that new collaborative research relationships have been formed as a result of

their interactions with a diverse, multi-disciplinary group of people involved in

all aspects of cancer research. 
•	 PRGs have led to the development of new information tools. Developed in 

response to needs identified by the groups, new tools are now available to aid 

both NCI staff and the community in learning about and responding to needs 

and opportunities for cancer research. For example, the Common Scientific 

Outline is a classification system that provides a consistent approach to 

comparing and assessing cancer research supported by different funding organizations. The Cancer Research Initiatives Website provides user friendly access 

to a database of selected NCI research funding opportunities that can be 

searched by type of research or type of cancer. And the Cancer Research 

Portfolio Website provides a structure for searching, organizing, and analyzing 

NCI-supported research by type of cancer and/or type of research. 

•	 PRGs have provided new opportunities for interaction between NCI and the 

extramural community. Participants have found the PRG venue a very effective 

way to gain input from the wider community and for individuals to influence 

both NCI priority setting and overall disease-specific priority setting. 

The NCI PRG process has been highly successful as a model for gaining outside input 

and feedback focused on opportunities, needs, and gaps in research and fostering 

greater understanding of common issues across diseases. Similar approaches 

have now been adopted by other research funders including the National Institute 

of Neurological Disorders and Stroke (Stroke Research), the National Institute of 

Diabetes and Digestive and Kidney Diseases (Bladder Disease Research), the National 

Institute on Aging (Exploring the Role of Cancer Centers for Integrating Aging and 

Cancer Research), the Department of Health and Human Services (Cancer Health 

Disparities), and the National Cancer Research Institute of the United Kingdom. 

Collaborations for Assessing PRG Recommendations 

NCI recognizes that research agendas developed by the PRGs are larger than we can 

address alone. Therefore, NCI works to engage other organizations that fund cancer 

research in addressing PRG recommendations and collaborating on relevant initiatives in order to leverage and optimize collective research efforts. To this end, NCI is 

bringing together groups of cancer funders to focus on joint implementation of 

research agendas. The objectives of these meetings are to: 

•	 Share and discuss information on ongoing and proposed initiatives related 

to specific cancers in order to identify common areas of emphasis, eliminate 

duplication, and address gaps in critical research areas. 

•	 Establish consensus on where the most serious gaps are and identify organizations that will be able to fill them. 

•	 Identify opportunities for collaboration or coordination in areas of mutual interest. 

•	 Establish a plan of action that includes mechanisms for continued communication and reporting on progress. 

•	 Optimize deployment of resources among participating groups. 

A Plan and Budget Proposal for Fiscal Year 2005 

DISEASE-SPECIFIC RESEARCH 

7 
I’m only 13 

years old, and 

now they tell me 

I have cancer? 

“I knew I was sick, but I 

thought I would just get 

better. I never thought about 

this. Almost nobody gets this 

disease. Is anybody working 

on a better treatment?” 

Ewing’s sarcoma is a rare 

malignant bone tumor that 

occurs in children and 

adolescents, with highest 

known incidence among 

Caucasian males. About 

150 new cases are reported 

each year in the United 

States. Prior to the new treatment regimen highlighted 

here, 50 to 60 percent of 

patients without metastases 

and about 25 percent with 

metastases have survived at 

least 5 years. 

The Sarcoma Progress Review Group 

In 2003, NCI launched a PRG to focus on sarcomas, a general group of less 

common cancers in which the cancer cells arise from or resemble normal cells in the 

body collectively known as “connective tissues.” Normal connective tissues include 

fat, blood vessels, nerves, bones, muscles, deep skin tissues, and cartilage. 

Sarcomas in general are rare tumors, accounting for less than five percent of adult 

malignancies and less than 20 percent of pediatric cancers. Nearly half of all sarcoma patients die of the disease. The most common forms of sarcoma include: 

•	 Soft tissue sarcomas that originate in connective tissues, fat, blood vessels, nerves, 

joints, muscles, cartilage, and deep dermal tissue. They occur more often in adults. 

•	 Osteosarcoma, which is the most common type of bone cancer. In children, it 

occurs most commonly in the bones around the knee. Although osteosarcoma 

occurs most often in adolescents and young adults, about 10 percent of cases 

develop in people in their 60s and 70s. 

•	 Kaposi’s sarcoma (KS), which usually develops in the skin or in the lining of the 

mouth, nose, or eye. In the last 20 years, the vast majority of KS cases have developed in association with human immunodeficiency virus (HIV) infection and 

acquired immunodeficiency syndrome (AIDS). 

As with past efforts, the Sarcoma PRG is soliciting extensive input from the research and 

advocacy communities and is examining the NCI’s research portfolio as well as research 

funded by other institutes and organizations for these cancers, with the goal of identifying scientific priorities and resource needs for making progress against all sarcomas. 

A written report describing the group’s findings and recommendations will be presented 

to the NCI and disseminated widely within the cancer community. The PRG will then 

meet with NCI leaders to discuss NCI’s plan for addressing the recommendations. 

Modified Chemotherapy Regimen Improves Survival for 

Ewing’s Sarcoma Patients 

Since the introduction in the 1970s of adjuvant chemotherapy for patients with 

Ewing’s sarcoma, survival rates for patients with this disease increased dramatically 

but are still considerably low. Recently, scientists have discovered that the addition of 

the drugs isofamide and eposide to standard chemotherapy seems to improve treatment outcomes for relapsed patients with either Ewing’s sarcoma or the closely related primitive neuroectodermal tumor of the bone. These findings led investigators to 

test this treatment regimen in newly diagnosed patients. Although outcomes for 

patients with metastatic disease were not improved, the added drugs significantly 

improved survival in patients with newly diagnosed nonmetastatic disease. After five 

years, 69 percent of patients who received the experimental drug regimen were disease free, compared to 54 percent of those treated with standard therapy. Overall five 

year survival was 72 percent in the experimental therapy group, compared with 61 

percent in the group treated with standard therapy. Although patients receiving experimental therapy suffered more infections and spent more time in the hospital, overall 

toxicity levels were similar between the two groups. These findings hold promise for 

patients with Ewing’s sarcoma and primitive neuroectodermal tumor of the bone. 

8 The Nation’s Investment in Cancer Research 
Optimizing New Knowledge and Opportunities 

Broad Research Priorities: 

NCI’s Action Plan for 2005 includes ongoing work in nine broad research priorities for focused efforts in core 

scientific and public health emphasis areas. Identified with assistance from our advisory boards, the larger 

research community, and the cancer advocacy community, these investments will allow us to accelerate 

the pace of discovery and to optimize use of existing and new knowledge for the development and delivery of 

evidence-based interventions. 

Core Scientific Reaching our Challenge Goal to eliminate the suffering and death due to cancer 

Areas will require long-term investment in large-scale and interdisciplinary studies to: 

•	 Understand the interactions between Genes and the Environment as they relate 

to cancer. 

•	 Elucidate the Signatures of the Cancer Cell and Its Microenvironment through 

a more integrative approach to cancer biology. 

•	 Validate and develop effective agents aimed at Molecular Targets of Prevention, 

Diagnosis, and Treatment. 

•	 Optimize Cancer Imaging and Molecular Sensing to both further research and 

allow for less invasive and more accurate cancer care. 

As we more fully understand cancer-related molecular, cellular, microenvironment, behavioral, psychological, and social influences, we can develop more effective and less harmful approaches to cancer prevention, early detection, diagnosis, treatment, and control. 

Areas of Public Purposeful investment must also be made for research and development in the 

Health Emphasis public health arena: 

•	 Tobacco and Tobacco-Related Cancers. We can no longer ignore the damage 

done by tobacco use in this country and the lure of smoking to our youth. 

•	 Energy Balance. We must face the issues of overweight and obesity and the 

sedentary lifestyle that is plaguing our country and raising people’s risk of developing cancer. 

•	 Quality of Cancer Care. We must work on behalf of the millions of people in 

our country today who do not receive appropriate care for their cancer. 

•	 Cancer-Related Health Disparities. Untold numbers of people suffer disproportionately from cancer and receive poorer care because of social position, 

economic status, cultural or language barriers, or geographic location. 

•	 Cancer Survivorship. The numbers of people surviving cancer have increased 

dramatically over the past several years. Sadly, a large portion of these people 

suffer post-treatment effects and do not receive the continued care they need. 

Investment in each of these areas is at the heart of our ability to reach our Challenge 

Goal to eliminate suffering and death due to cancer. In each instance, we need better science to understand the complexities. And there is a pressing need to address 

the challenges posed to our Nation's healthcare system by the rising incidence of 

cancer in the aging U.S. population. For all Americans, we need evidence-based 

interventions that will prevent cancer from occurring and improve the health and 

quality of life for those who are affected by cancer. 

BROAD RESEARCH PRIORITIES 

A Plan and Budget Proposal for Fiscal Year 2005 9 
10 The Nation’s Investment in Cancer Research

Genes and the Environment 

Cancer is a complex disease that develops when errors occur in a person’s genes. Some of these

genetic errors are inherited. Others result from certain environmental exposures or individual behaviors, usually coupled with inherited susceptibility. Through the use of increasingly sophisticated molecular technologies and the tremendous resource generated by the mapping of the human genome, 

scientists now know that some inherited genetic errors nearly always give rise to cancer, regardless of

a patient’s environmental or lifestyle history. For example, carriers of mutations in the gene for familial

adenomatous polyposis are almost certain to develop colon cancer. Other mutations present at birth

only lead to cancer in combination with certain environmental exposures. This relationship is seen in

women with BRACA mutations, who are at increased risk for hormonally induced breast cancers. Still

other cancers are caused by long-term damage to multiple genes caused by environmental factors,

with some people inherently at higher risk than others. For instance, people with certain combinations

of genetic mutations to the NAT2 gene are at increased risk for smoking-related bladder cancer. 

New tools and technologies are helping us to better assess who is at risk for specific

cancers based on genetic makeup and environmental exposures. Furthermore, we are

increasingly able to identify and assess a variety of carcinogenic exposures encountered outdoors, in the home, and in the workplace. These include pollutants in air,

water, and soil; components of food, tobacco, alcohol, and drugs; sunlight and other

forms of radiation; and infectious agents. Other new technologies are revealing the

intricate biological processes involved in the development of cancer.

To build on this progress, NCI must continue to develop novel ways to study the

complexities of genetic and environmental contributions to cancer. We must support

both individual efforts and large collaborative programs to maximize the availability of population data, biospecimens, laboratory models, and in vitro observations.

In particular, large-scale studies with new levels of interdisciplinary cooperation and

innovation are needed. These investments will help scientists uncover environmental

risk factors, identify genetically susceptible individuals, develop appropriate interventions and precautions for people at high risk, and generate new individual and

public health strategies to avoid adverse exposures.

PROGRESS IN PURSUIT OF OUR GOAL

Building Capacity through Large-Scale Collaborations

NCI continues to promote collaboration through cohort consortia, bringing

together researchers across the United States and Europe who are studying the

same disease site to collaborate and pool exposure data and biospecimens. This

type of data pooling is essential for detecting patterns. The Cohort Consortium

for Breast and Prostate Cancer pioneered the approach and developed the

Hormone-Related Gene Variants program to identify genes that may influence a

person’s susceptibility to hormone-related breast or prostate cancer and to develop methods of data sharing across genome and genotyping centers, removing a

major obstacle to consortium research. 

Discovery

Scientists have developed

technologies to compare

complex profiles of genes

and proteins from cancer

patients to corresponding

profiles of cancer-free individuals. This innovation is

helping to identify specific

molecular profiles associated

with cancer risk. 

NCI is pursuing research

opportunities in several

growth areas to better

understand cancer-related

genes, environmental and

lifestyle factors, and their

interactions. 
NCI and NIEHS collaborations encourage the 

development and use of 

innovative methods for 

assessing difficult to 

measure environmental 

exposures. 

NCI also supports development of case-control consortia composed of epidemiologic investigators studying less common cancers. For example, the InterLymph 

Consortium is studying the genetic and environmental basis of non-Hodgkin’s 

lymphoma. Another consortium is focusing on brain tumors. Members of the 

NCI-supported Health Maintenance Organization Cancer Research Network are 

pooling their resources to develop the largest ever case-control study of pancreatic 

cancer. In addition, we are examining the feasibility of a cohort study in India to 

focus on nutrition and gene-diet interactions in cancer causation. 

Assessing and Measuring Environmental Exposures 

NCI and the National Institute of Environmental Health Sciences (NIEHS) continue to support interdisciplinary collaborations for improving research tools used in 

etiologic studies of cancer and risk assessment. For example, these institutes are 

funding centers for the study of breast cancer risk associated with environmental 

exposures and several projects to support the use of geographic information systems in 

cancer epidemiology and control studies. 

NCI scientists are using innovative nanotechnologies in molecular profiling to 

examine chromosomal alterations and changes in protein levels following exposure 

to environmental carcinogens. For example, scientists have found that changes in the 

levels of proteins following alteration of their gene precursors by the biochemical 

process of methylation are associated with the development of cancer. 

Discovering and Characterizing Cancer Predisposing Genes in 

High-Risk Families 

NCI’s Interdisciplinary Studies in the Genetic Epidemiology of Cancer emphasize 

case-control and familial studies of gene-environment interactions for various forms 

of cancer. NCI-supported work includes a consortium of investigators searching for 

pancreatic cancer susceptibility genes, the Colon, Breast, and Ovarian Cancer 

Family Registries (CFRs), a high-risk families tissue resource, and other family registries and collaborative groups working to identify susceptibility genes for prostate 

cancer and other familial cancer syndromes including melanoma, renal cancer, 

testicular cancer, and brain tumors. 

The Cancer Genetics Network (CGN) is a major NCI-supported infrastructure for 

studies of persons at high risk for developing cancer and for related translational 

research. CGN pilot studies combine existing and prospectively collected data 

to discover potentially important gene-environment interactions. The Network 

holds epidemiologic data on participants consistent with data collected by other 

NCI-supported consortia and registries, allowing the information to be used either 

independently or in combination with other groups. The CGN implemented and 

improved upon a state-of-the-art clinical trials informatics system (Trial-DB) 

across all Network sites. 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 11 
Developing and Improving Resources for Gene Discovery and 

Characterization 

NCI is providing readily available resources to support researchers studying geneenvironment interactions in cancer causation, including the following: 

•	 The Cancer Genome Anatomy Project (CGAP) continues to provide genomic 

resources for identifying and studying cancer genes. For example, CGAP’s 

Mammalian Gene Collection establishes reference clones validated by sequence 

analysis for research use and has importance for both in vitro and populationbased studies. The SNP500 program provides sequence verification of single 

nucleotide polymorphisms (SNPs). SNP500 will also develop assays for the 

Cohort Consortium, making all information immediately available on the Web. 

(For more information on these and other CGAP programs, see pages 16-17.) 

CGF researchers develop • NCI has developed a high-throughput Core Genotyping Facility (CGF) to supand validate assays for port case-control and cohort studies in partnerships with the National Human gene sequence verification 

in conjunction with the	 Genome Research Institute, the Centers for Disease Control and Prevention, 

SNP500 cancer program. 	 and academic and commercial organizations. The CGF provides high-throughput genotyping and gene sequencing, including verification of SNPs and other 

types of genetic variations. The Facility is also a test site for the development of 

policies, systems, and infrastructure to expedite data analysis of large-scale 

interdisciplinary studies and to enhance data sharing. 

•	 CGN has substantially increased the number of participating patients and family members in its biospecimen repository. 

•	 CFRs are developing a repository of EBV-transformed cell lines1 from patients 

and selected family members for use by researchers. 

•	 The Gail Model is a statistical tool to help estimate a woman’s risk of breast 

cancer based on a number of predisposing factors, including family history. A 

study examining mammographic density as a risk factor for breast cancer 

development was completed recently, showing this characteristic reliable 

enough to be formally included in the model. 

•	 NCI continues to support workshops to develop collaborative studies between 

population scientists and groups developing mouse models of cancer for the 

localization and characterization of cancer susceptibility genes. 

Improving Quality Control Measures to Maximize the Value of Specimens 

Biological specimens collected from patients, people at risk for cancer, and their families must be processed and stored according to strict requirements. This level of care 

is needed to ensure that the specimens are of sufficient quality to be used in a wide 

variety of assays and test procedures. NCI and partners are helping to develop and 

disseminate procedures to safeguard the quality of such samples. For example: 

•	 CFRs support academic-commercial biotechnology partnerships to establish an 

integrated and standardized infrastructure for the collection and management 

of biospecimens from large populations, the production of related microarrays, 

and the development of novel relational data management software for associated molecular, clinical, and risk factor data. 

1 Cells taken from individuals normally do not live long in vitro. Cells “transformed” by in vitro infection with Epstein-Barr 

virus (EBV) will live and replicate indefinitely, providing a ready supply for research. 

12 The Nation’s Investment in Cancer Research 
•	 CGF activities include sponsorship of conferences on specimen handling and 

quality control for DNA storage and analysis. 

•	 NCI’s intramural Epidemiology and Carcinogenesis Faculty has sponsored 

national workshops on how to process specimens to optimize their use in conjunction with current technologies. This faculty also helped found the 

International Society for Biological and Environmental Repositories, which developed a “best practices” document for the collection and storage of specimens. 

•	 A series of NCI-supported studies have established an optimal protocol for collecting oral epithelial cell samples for genetic testing from large populations by 

mail, and pilot work has established acceptably high rates of compliance by 

study populations. Progress has been made in addressing issues of potential 

DNA damage by irradiation of samples during transport through the mail. 

•	 The NCI Center for Bioinformatics has recommended a set of informatics standards, guidelines, and procedures for handling and storage of biospecimens. 

Development	 Supporting Intervention Trials and Translational Research on 

Inherited Susceptibility 

NCI scientists and CGN are conducting a collaborative, prospective study of risk 

reduction in women at high genetic risk for breast and ovarian cancers. Researchers 

are comparing and evaluating two risk reduction strategies: preventive removal of 

the ovaries and fallopian tubes and a novel screening strategy. Investigators will 

include the impact of these procedures on quality of life in their evaluation. 

NCI is also collaborating with the National Surgical Adjuvant Breast and Bowel 

Project to genotype participants in the Breast Cancer Prevention Trial, which 

showed that tamoxifen reduced the risk of breast cancer among high-risk women. 

Collaborators will focus on determining if variants in genes related to estrogen and 

tamoxifen metabolism can identify subsets of women who might be more or less 

likely to benefit from tamoxifen. 

NCI is researching alternative screening techniques for early breast cancer detection 

in women genetically at risk for the disease. These include magnetic resonance 

imaging (MRI), positron emission tomography (PET) imaging, and in vitro analysis 

of cells obtained from breast duct lavage. 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 13 
GENES AND THE ENVIRONMENT 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Discover those genetic, Discovery 

environmental, and 1. Identify susceptibility genes, haplotypes, and epigenetic events, and their 

lifestyle factors and interactions with environmental factors in cancer causation. $32.00 M 

their interactions that ■ Continue to investigate interactions among susceptibility genes, haplotypes, and environmental risk 

define cancer risk factors through support to the Cohort Consortium: 

and that can inform — Plan and support studies of additional cancer sites, using the results of the study of hormonethe development and related variants and breast and prostate cancer. $5.00 M 

delivery of new strate­ — Increase the number of study participants and cancer types, enhance population diversity, and gies for prevention, augment the biospecimen repository by continuing to expand the number of participating 

early detection, and cohorts. $3.00 M 

treatment. 

■ Continue to investigate gene-environment interactions in lymphoma, brain, melanoma, prostate, and 

other selected cancers through case-control consortia. Fully support population-based and hospitalbased studies to analyze pooled data for genetic and environmental susceptibility factors. $1.00M 

■ Conduct new initiatives in resequence analysis of genes chosen from known biological pathways or 

identified by microarray expression or comparative genomic hybridization analysis. 

■ Study cancers of high lethality by combining data from several studies using a consortial approach. 

$15.00 M 

■ Study populations at low risk of cancer to identify genes that may confer resistance to tumor development and environmental factors that may modulate the effect of these genes. $8.00 M 

■ Provide a forum for developing innovative new investigations through a consortium of groups capable 

and willing to conduct site-specific, case-control, and consortial studies. 

2. Develop new ways to assess and measure environmental exposures for use in 

population studies. $6.00 M 

■ Continue to develop new noninvasive techniques for collecting and analyzing genes and gene products 

in very small biologic samples by expanding the Innovative Molecular Analysis Technologies Program. 

$2.00 M 

■ Continue to apply and validate measures of the cumulative cellular, genetic, and molecular effects 

of environmental exposure through funding supplements for ongoing research programs. $3.00 M 

■ Develop improved measures of nutrition and energy balance and of components of tobacco use. 

$1.00 M 

3. Identify cancer predisposing genes in high-risk families and investigate how 

other genes and environmental factors modify expression of these genes. $11.00 M 

■ Extend studies and the geographical and population diversity of registries for familial cancers as well as 

additional heritable cancer sites in the United States, in cooperation with the Surveillance, Epidemiology, 

and End Results Program (population data) and Cancer Centers/Specialized Programs of Research 

Excellence (patient data). $4.00 M 

■ Expand the family registries for breast, ovarian, and colon cancers. $7.00 M 

14 The Nation’s Investment in Cancer Research 
4. Develop and improve tools and infrastructures for the study of geneenvironment interactions in human populations. $11.00 M 

■ Continue to maximize the quality, efficiency, and cost-effectiveness of specimen collection, processing, 

storage techniques, and high-throughput assays for human population studies and develop pilot feasibility projects for regional genotyping facilities. $3.00 M 

■ Develop with other NIH institutes a comprehensive informatics system to capture store, analyze, and 

integrate the expanding amount of information generated by studies of gene-environment interactions. 

$4.00 M 

■ Accelerate identification, validation, and development technologies for genetic epidemiology studies 

through the Cancer Genome Anatomy Project. $1.00 M 

■ Facilitate the localization of cancer susceptibility genes in humans and determine their function, by supporting the Mouse Models of Human Cancers Consortium, which has targeted mouse models in breast, 

colon, prostate, and pancreatic cancer. $3.00 M 

Development 

5.	 Support collaborative studies of high-risk individuals to address the clinical, 

behavioral, and societal issues associated with cancer susceptibility. $12.00 M 

■ Facilitate studies of outcomes for early detection, diagnosis, and treatment of genetically high-risk individuals, especially those from minority and underserved populations, through resources provided by the 

Cancer Genetics Network. 

■ Expand development of effective strategies to communicate cancer risk information to high-risk 

persons, patients, healthcare providers, and the public and maximize the recipients’ abilities to make 

decisions and choices. $4.00 M 

■ Refine cancer risk prediction methods/models to integrate genetic and environmental determinants of 

cancer among diverse populations. $1.00 M 

■ Study the screening and treatment choices and preventive and other health behaviors of cancer 

survivors and persons at known genetic risk or in families with a high prevalence of cancer. $2.00 M 

■ Conduct observational studies, and trials where appropriate, of the long-term risks and benefits of currently used cancer risk reduction strategies (e.g., surgical, drug) for genetically high-risk individuals. 

$5.00 M 

Management and Support 	 $ 1.15 M 

Total $73.15 M 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 15 
16 The Nation’s Investment in Cancer Research

Signatures of the Cancer Cell and Its Microenvironment

Thirty years ago, cancer was a poorly understood, and usually deadly, disease. Today, we have a far

better understanding of how cancer develops and progresses within the human body. We know that

a cell becomes malignant as a result of changes to its genetic material and that accompanying biological characteristics of the cell also change. These changes form unique, measurable molecular

“signatures” that signal the presence of disease. This more robust understanding of the genetic

changes within a cancer cell — and the resulting changes in the production and function of proteins

— has altered the course of cancer research and has fueled new approaches to prevention, detection,

diagnosis, prognosis, and treatment. 

Scientists also realize, however, that they cannot view cancer as a self-contained collection of malignant cells but must consider the integral association of the cancer

with its host environment. This “tumor microenvironment” includes a variety of cell

types, their behavior often altered through interaction with the cancer cells. The

microenvironment is also rich in growth factors and enzymes and includes parts of

the blood and lymphatic systems. Dynamic interactions between the cancer cell and

its microenvironment can contribute to some of the most destructive characteristics

of cancer, including metastasis. The microenvironment can also influence the access

of therapeutic agents to tumor cells, the body’s processing of treatment agents, and

the development of resistance to cancer treatments. Both cancer cells and their surrounding environment need to be fully characterized in order to understand how

cancer grows in the body, and both need to be considered when developing new

interventions to fight the disease. 

The interactions between cancer cells and their microenvironment permit, and even

encourage, cancer progression. Scientists are deciphering the signatures of cancer

cells, those of seemingly normal cells in the tumor microenvironment, and signatures

that reflect changes that occur as cancer cells interact with the host environment.

PROGRESS IN PURSUIT OF OUR GOAL

Searching the Genome for Cancer Signatures

All Cancer Genome Anatomy Project (CGAP) data and resources are readily available to the biomedical research community, enabling researchers to find “in silico”

answers to biological questions in a fraction of the time it once took in the laboratory. In 2003, CGAP and its private, academic, and industry partners made several

new resources available to the research community. 

• Through the SAGE Genie Anatomic Viewer, a scientist can identify the genes uniquely expressed in specific cancers. One team of researchers has used this tool to identify

a gene previously known to be overexpressed in prostate cancer that also appears to

be a marker for metastatic breast cancer (cgap.nci.nih.gov/SAGE/AnatomicViewer).

• Through the CGAP SNP500 Cancer Project, scientists are currently examining

samples taken from individuals of four ethnic groups to find known or newly

discovered single nucleotide polymorphisms (SNPs) of immediate importance to

molecular epidemiology studies in cancer (snp500cancer.nci.nih.gov/home.cfm).

NCI’s long-range goal for 

signatures research is to

characterize the interactions

between a tumor and its

microenvironment and 

these with the entire body.

Defining more fully this range

of molecular signatures for

cancer will dramatically

increase our understanding 

of cancer development,

detection, diagnosis, and

prognosis and lead to the

identification of new targets

for prevention and treatment. 

Discovery and

Development

Cancer researchers continue

to make significant progress

in understanding the genetics

and biology of precancerous

and cancerous cells and cells

within the tumor microenvironment. They are defining

the molecular signatures of

these cells and identifying

those that can be used as

markers for early detection,

diagnosis, or prognosis or be

targeted by new interventions

for prevention or treatment. 
CGAP and private-sector 

Affymetrix scientists are collaborating to develop a new 

technological approach that 

will ultimately enable cancer 

researchers to peer more 

deeply and broadly into gene 

expression changes in cancer. These scientists have 

produced whole chromosome chips for chromosomes 21 and 22, allowing 

researchers to look at genetic activity in all regions of 

these chromosomes, and 

have discovered thousands 

of previously unknown 

regions that contain coding 

for proteins. This approach 

may also provide a valuable 

tool for discovering “hidden” 

RNA activity that may have 

an important structural or 

regulatory role in the cell. 

•	 SAGE Genie is an informatics system that provides a view of all CGAP data produced through the Serial Analysis of Gene Expression (SAGE) approach. SAGE 

can be used to distinguish normal cells from tumor cells and to reveal potential 

markers for detection or diagnosis. 

•	 CGAP scientists have collaborated with scientists from Lynx Pharmaceuticals, the 

Ludwig Institute, Duke University, and Johns Hopkins University to use a new technique known as Massively Parallel Signature Sequencing (MPSS) to study genes that 

are expressed at relatively low levels, as well as functional relationships among genes, 

greatly increasing our ability to find all the genes that are important to cancer. 

Searching the Proteome for Cancer Signatures 

Proteomics, the comprehensive study of proteins and their functions, is an important complement to studies exploring the genetic changes associated with cancer. 

Scientists at NCI and the Food and Drug Administration (FDA) are working together 

through the Clinical Proteomics Program (CPP) to explore complex protein patterns 

and define protein profiles that can be used for early detection, diagnosis, prognosis, 

and treatment monitoring. 

•	 CPP scientists are developing a screening test for ovarian cancer that has demonstrated an ability to successfully use complex protein pattern analysis to distinguish with 100 percent accuracy between ovarian cancer patients and unaffected persons. A refined test even promises to accurately detect Stage 1 ovarian cancers, a 

potentially curable stage for which no reliable screening tool is yet available. 

•	 CPP investigators are examining serum protein patterns that may someday help 

clinicians determine whether men with mildly elevated prostate-specific antigen 

(PSA) levels have prostate cancer or need no further diagnostic analysis and 

treatment. Such a test could save many men from having to undergo biopsy and 

help them make more informed decisions about “watchful waiting.” Similar 

studies are being conducted to identify protein profiles for detecting and diagnosing pancreatic, breast, and lung cancers. 

Providing Resources for Molecular Profiling 

Scientists now have the tissue microarray tool as a quick and cost-effective means 

of performing automated, high-throughput analyses of multiple cancer tissues and 

can use that information to develop and validate molecular profiles of tumor cells. 

Microarray slides contain as many as a thousand tissue specimens of a specific cancer and can be used to determine whether specific genes are valuable biomarkers for 

cancer and whether the protein encoded by the candidate gene affects the tumor’s 

behavior and holds potential as a molecular target for treatment. Researchers can 

use microarray technology to perform the equivalent of hundreds of experiments 

simultaneously. The Tissue Array Research Program (TARP), a collaborative effort 

with the National Human Genome Research Institute, has allowed one research 

team to study the Akt oncogene, which encodes a protein that blocks programmed 

cell death and its signaling pathway in different types of tumor cells. These investigators found that cellular signaling through this pathway varied among different 

tumor cells, suggesting tumor type-specific targets for therapy and highlighting the 

complexity of signaling pathways in human tumors. 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 17 
Several researchers are developing microarrays and nanotechnologies such as 

carbon nanotubes, nanowires, microcantilevers, and quantum dots through 

NCI’s Innovative Molecular Analysis Technologies (IMAT) program. These 

molecular sensing tools can be used to analyze interactions among proteins, perform molecular classification of tumors, conduct high-throughput screening, and 

predict therapeutic efficacy. 

Using Molecular Signatures for Early Detection of Cancer 

Scientists in the Early Detection Research Network (EDRN) have applied advances 

in genomics and proteomics to discover a variety of promising biomarkers including two genes unique to ovarian cancer, chemical modification (methylation) of 

specific genes predictive of lung cancer, and protein patterns predictive of prostate 

cancer. They are also applying a recently formulated roadmap outlining the five key 

phases of biomarker development to evaluate microsatellite instability as a marker 

for recurrent bladder cancer. Similar tests may eventually be developed for screening other cancers that shed cells into body fluids, such as tumors of the oral cavity 

and the gastrointestinal tract. 

Developing Better Classification Schemes to Improve Diagnostic Tests 

Researchers supported through the NCI Director’s Challenge: Toward a Molecular 

Classification of Tumors (dc.nci.nih.gov) use comprehensive molecular analysis

technologies to help scientists identify better strategies for classifying tumors and in 

turn allow for more accurate diagnosis and prognosis as well as the opportunity to 

select therapies tailored to individual patients through the targeting of specific 

molecular features. Director’s Challenge investigators recently studied the gene 

expression patterns of ovarian cancer tumors to develop a molecular classification. 

Their classification provided insight into why some subtypes have a worse prognosis than others. This type of gene profiling may lead to improved patient diagnosis 

and prognosis for a broad range of cancers and provide clues for identifying molecularly targeted interventions. 

Using Molecular Signatures to Study Models of Human Cancer 

In less than 4 years, Mouse Models of Human Cancers Consortium (MMHCC) 

investigators have rapidly evolved a suite of novel approaches for mouse germline 

engineering and biological analysis. These fundamental advances are furnishing the 

research community with cancer-prone strains that not only accurately mimic 

human cancers but also support unprecedented discoveries about these cancers. 

One research team made an important discovery using a mouse model for human 

breast cancers caused by overexpression of the gene c-Myc. They identified a gene 

expression pattern in these animals that has also been found in human c-Mycrelated breast cancers. This finding provides valuable clues for distinguishing 

among human cancer subtypes. Comparable studies on models of other malignancies are underway with similar results. 

18 The Nation’s Investment in Cancer Research 
19 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

found only in women infected with human papillomavirus, was once the most common 

• 

• 

• 

• 

studying the natural history of this virus, how the virus is transmitted between 

• 

• 

page xix.) 

Cervical cancer cell. 

an uneven surface with many 

which may enable it to be 

divide rapidly in a chaotic 

clump to form tumors 

which may invade and 

Cancer of the cervix (the 

neck of the uterus or womb) 

is one of the most common 

Attacking the 

A Plan and Budget Proposal for Fiscal Year 2005 

Studies suggest that as many as 15 percent of all cancers worldwide may be caused, 

at least in part, by viral infections. Clearly, effective prevention and treatment interventions aimed at these cancers are critical to reducing the cancer burden. The drastic 

reduction in cervical cancer mortality since 1955 is one success story. This disease, 

cancer killer of women. Thanks to detection of virus-related lesions by Pap testing, this 

disease can now be detected early and is highly curable. However, with the advent of 

the HIV/AIDS pandemic, certain virus-related cancers are becoming more prevalent, 

both nationally and worldwide. Immunocompromised HIV/AIDS patients are vulnerable 

to infections and associated cancers that healthy individuals would easily resist. 

To successfully address cancers caused by viral infection, we must learn more about 

the biological mechanisms of their development and progression and apply this knowledge to develop effective treatment and prevention measures. Highlighted below are a 

few recent NCI-supported national and international collaborations that are providing 

greater insights into virus-related cancers. 

Human papillomavirus is the primary cause of cervical cancer. Investigators are 

developing a vaccine to prevent cervical and other cancers caused by this virus. 

Epstein-Barr virus (EBV) infection, although usually benign, can promote aggressive 

lymphomas, soft tissue tumors in HIV-infected children, and other tumors. 

Researchers are studying the epidemiology of EBV-related tumors and are developing novel therapies including strategies that harness the immune system to attack 

cancer cells. Investigators are also exploring a possible link between EBV and some 

aggressive breast cancers. 

Infection with hepatitis virus B or C increases a person’s risk of developing liver 

cancer. Scientists are investigating how genetic and environmental factors interact to make some infected individuals more at risk than others. 

Human T-cell lymphotropic virus causes adult T-cell leukemia. Investigators are 

individuals, and risk factors for cancer progression. 

Human herpesvirus-8 (HHV-8) is associated with Kaposi’s sarcoma and aggressive 

lymphomas, particularly in HIV-positive individuals. Scientists are examining the epidemiology of this virus, identifying routes of transmission, researching strategies to 

prevent infection and tumor development, and developing novel therapies for 

Kaposi’s sarcoma and other tumors caused by HHV-8. 

Investigators are developing better treatments for AIDS-related lymphomas, 

making this previously universally fatal disease highly curable in many patients. (See 

This large rounded cell has 

cytoplasmic projections, 

motile. Typically, cancer 

cells are large and they 

manner. Cancer cells may 

destroy surrounding tissues. 

cancers affecting women. 

Research on Cancer 

and Viruses — 

Cancer Burden 
SIGNATURES OF THE CANCER CELL AND ITS MICROENVIRONMENT 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Accelerate our Discovery 

progress in under­ 1. Define the molecular signatures of cells in the cancer microenvironment at 

standing the dynamic various points during the initiation and progression of cancer. Compare the 

interaction between molecular signatures of stromal and cancer cells during development and 

cancer cells and their aging. $9.50 M 

microenvironment and ■ Promote the analysis of cancer as a complex biological system by establishing an Integrative Cancer 

our application of this Biology Program, with the ultimate goal of developing reliably predictive models for “in silico” develknowledge to the opment of cancer interventions. $2.00 M 

detection, diagnosis, ■ Provide a focus for research into the dynamic interaction between cancer cells and their microenviprevention, treatment, ronment and a forum for the exchange of information and resources by supporting a series of new 

and control of all initiatives relating to the microenvironment of tumors. $3.50 M 

cancers. ■ Facilitate the analysis of normal and cancerous cell samples for signature profiling studies by establishing a national core facility. Develop a database of the molecular signature profiles of cells in the 

microenvironment and make these data readily available to the research community. $1.00 M 

■ Advance the development of nanoparticles, molecular beacons, and high-resolution sensors for 

cancer signature detection, targeting, and treatment from the development stage into clinical trials 

and translation into the clinic, through expansion of the Unconventional Innovations Program (UIP). 

$1.50 M 

■ Expedite the translation of micro- and nanotechnology tools for detecting molecular signatures of 

cancer and monitoring major signal transduction networks into products that can be used in clinical practice, through expansion of the Innovative Molecular Analysis Technologies Program (IMAT). 

$1.50M 

2. Define the dynamic communications among cancer cells, surrounding cells, 

and immune cells that control or promote primary and/or secondary tumor 

growth. Characterize the interaction between the immune system and the cancer cell during cancer initiation and progression. $8.00 M 

■ Identify the factors used by cancer cells to activate cells in the tumor microenvironment that support tumor growth and progression. Encourage studies that explore the unique role the bone 

microenvironment plays in metastasis of cancer to bone, focusing in particular on breast cancer, 

prostate cancer, and myeloma. $3.50 M 

■ Identify the origin of the cells and factors that comprise the tumor microenvironment. $2.00 M 

■ Develop organotypic culture systems that accurately model the interaction between the cancer cell 

and the tumor microenvironment in living systems. Make these systems readily accessible to the 

research community. $1.00 M 

■ Identify the molecular composition and physiological or pathological contributions of extracellular 

matrix components to biological properties such as survival, proliferation, and migration of normal 

and malignant cells. $1.50 M 

20 The Nation’s Investment in Cancer Research 
3. Support new approaches to provide the research community with 

rapid access to validated reagents. $7.00 M 

■ Establish a repository for antibodies, cell lines, animal models, and tissues that relate to 

cells in the microenvironment. $2.00 M 

■ Establish a database that includes comparisons of cellular interactions between cancer cells 

and surrounding cells in animal models and in humans. $1.00 M 

■ Identify proteins and proteomic signatures in microdissected tissue samples of human cancers (normal epithelium, premalignant lesions, adjacent tissue, and invasive tumors) 

through expansion of the Clinical Proteomics Program. $4.00 M 

4.	 Stimulate progress in understanding the role of stromal cell interactions in cancer development by establishing a spectrum of educational 

and communication initiatives involving scientists across disciplines 

and with a broad range of expertise. $4.00 M 

■ Encourage multi- and trans-disciplinary investigations by establishing a new funding mechanism to allow co-investigators from different scientific fields to submit a collaborative grant 

application. $2.00 M 

■ Develop training curricula for students and established investigators and facilitate the development of novel studies in understanding the role of cellular interactions in cancer development, by establishing national trans-disciplinary training centers. $2.00 M 

Development 

5.	 Create targeted interventions by applying knowledge of cellular interactions in cancer development derived from profiling studies that 

explore cell-microenvironment interactions. $6.00 M 

■ Efficiently develop new drugs that target cells in the microenvironment, and move them into 

clinical use by initiating a Rapid Access to Intervention Development-type program. 

$1.00 M 

■ Develop new “targeted” reagents, including small molecules, RNAi, and antibodies through 

supplemental funding to NCI-funded investigators. $1.00 M 

■ Visualize the physiologic, cellular, and molecular processes in living tissues through functional and molecular imaging studies. These studies will focus on (1) identifying the subtle 

and important early changes in the molecular biology of tumors and the microenvironment 

as tumors become malignant, and (2) monitoring the effects of therapy on tumor cells and 

the tumor microenvironment. $4.00 M 

Management and Support 	 $ 0.80 M 

Total $ 35.30 M 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 21 
22 

i

1 

dence to support Vi

ducing a favorable growth environment, stimulating DNA instability and damage, 

About 15 percent of cancers throughout the world are linked to infectious agents that 

provoke chronic inflammation — for example, Heliobacter pylori with gastric cancer 

with chronic inflammation caused by long standing exposure to chemicals such as those 

found in cigarettes or asbestos. But the most established and elucidated connection 

Drug Therapy Establishes the Link 

Evidence supporting a link between chronic inflammation and colon cancer came together 

long-term chronic inflammatory bowel disease, a group of disorders causing chronic and 

Population studies confirmed this association. At the same time, scientists studying the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) were also finding evidence to support this link. 

In a 1980 animal study and a 1983 case study in humans, scientists observed that NSAIDs 

Several studies reported reduced rates of colorectal cancer in arthritis sufferers who treated 

their pain with daily doses of aspirin and other NSAIDs. And two large population studies 

found that regular use of NSAIDs over several years reduced the occurrence and mortality 

for colorectal cancer in the populations studied. The weight of this collective evidence 

prompted various research teams throughout the country to explore how NSAIDs act on 

the body and how this action results in reduced polyp growth and colon cancer risk. 

ties and adverse side effects, it was assumed that they also share a common mode of action. 

1 

infection. It is characterized by increased blood flow to the injured site, redness, swelling, elevated temperature, and pain. 

Story of Discovery 

BENEFITS FOR CANCER 

like substance that influences 

modulation of inflammation. 

Magnification: 10x. 

The Nation’s Investment in Cancer Research 

Nearly 150 years ago, the German physician Rudolph Virchow first proposed a connection between 

inflammation and cancer. Noting that cancerous tissue also contains the cells and factors that are hallmark features of the body’s inflammatory response, V rchow hypothesized that cancer begins at sites of 

chronic inflammation. At the time — and for many years to follow — the scientific community disavowed 

this idea because few could envision how the body’s first line of defense against tissue injury and infection could also cause harm. Over the past decade, however, scientists have uncovered increasing evirchow’s claim. They have determined that the very factors recruited by the body to 

prevent infection and encourage healing at an injured site can misfire and produce damage. And, if the 

triggering bacteria, virus, or chemical irritant lingers in the body, a state of chronic inflammation can arise. 

Today, research indicates that chronic inflammation underpins a host of diseases, including cancer. Studies have shown that inflammatory cells promote tumor growth by proenabling blood vessel development (angiogenesis), and facilitating the spread of cancer. 

and hepatitis B and C viruses with liver cancer. In addition, cancer may be associated 

between chronic inflammation and cancer is with colorectal cancer. 

from multiple paths of scientific discovery. For years, scientists observed that patients with 

recurring inflammation of the intestines, often develop colorectal cancer. 

NSAIDs, which include aspirin, are among the oldest and most widely used drugs in history. 

caused the regression of intestinal polyps — non-cancerous growths that often lead to cancer. 

The Search for a Common Thread 

With a chemically diverse group of drugs like NSAIDs sharing the same therapeutic qualiThe activity of these drugs was determined in 1971 when Dr. John Vane and his colleagues 

demonstrated that aspirin and all NSAIDs restrict inflammation by inhibiting the body’s 

production of prostaglandins. Vane predicted that NSAIDs accomplish this outcome by 

Inflammation is the body’s natural response to the tissue injury caused by a wound or bacterial, viral, or parasitic 

ANTI-INFLAMMATORY THERAPEUTICS MAY PROVIDE SECONDARY 

Polarized light micrograph 

(PLM) of prostaglandin B1. 

Prostaglandin is a hormonemetabolism, blood pressure, 

smooth muscle activity, and 
23 

blocking the activity of the cyclooxygenase (COX) enzyme, which catalyzes a key step in 

studies confirming the role of COX enzymes in prostaglandin production, and ultimately 

for the development of drugs that treat inflammatory diseases by blocking the activity of the 

research teams became interested in a protein produced by cells that were becoming cancerous. Through further research, they found the gene responsible for producing this protein, and noted it was related to the COX enzyme. Naming the new protein COX-2, the 

scientists determined that it is activated only during inflammation, while the “original” 

COX-1 enzyme is present in cells at all times and functions to protect the lining of the stomach and intestines by stimulating mucous production. 

Scientists recognized that NSAIDs reduce inflammation by blocking the actions of the 

COX-2 protein, making them potent treatments for inflammation-associated diseases like 

arthritis. But they still did not have the findings to document why these anti-inflammatory agents reduce colorectal cancer risk. In 1994, a key piece to this puzzle — the link 

between COX-2 and colorectal tumors — was provided by Charles Eberhart and 

Raymond DuBois who observed that COX-2 (but not COX-1) levels are elevated in as 

many as 80 percent of colorectal tumors. This finding, since replicated by animal studies, suggests a role for COX-2 and inflammation in tumor development. 

The potential of NSAIDs as chemoprevention agents for colon cancer is considerably limited by the fact that these drugs can cause serious adverse effects. Because they block the 

actions of both COX proteins, dosing can lead to excessive stomach acid production, ulceration, and gastrointestinal bleeding. Scientists thought that a better chemoprevention drug 

would need to selectively target only the COX-2 enzyme, thereby reducing the most harmful effect of NSAIDs while capitalizing on their benefits. In a milestone NCI-sponsored cancer prevention trial, researchers reported on such a drug, celecoxib, an arthritis medicine 

that selectively targets the COX-2 enzyme, substantially reducing the number of polyps in 

patients with an inherited disorder of the colon and rectum which causes polyp growth and 

pancreas. Based on this information, through 11 clinical trials, scientists are now working 

to determine if these tumors may be vulnerable to the effects of COX-2 inhibitors. 

the recurrence of colon polyps among people with previous colon cancers or polyps. These 

data suggest that daily aspirin may be an appropriate supplement to regular surveillance 

procedures in individuals who have an increased risk for colon cancer that is similar to the 

level of risk among the trial participants. It is important to note that long-term aspirin 

therapy is not appropriate for everyone: most people do not have the same elevated risk 

for colon cancer as those observed in these clinical trials. In addition, aspirin, like many 

drugs, can have side effects. All people age 50 and older should continue to get colorectal 

Colonic polyp. Colonoscope 

(endoscope) view of a benign 

(large intestine). This is a 

tubulovillous adenoma, a 

lial tissue lining an organ. 

stalk, this type (tubulovillous) 

forms in a tube shape. If the 

polyp causes discomfort, or 

it is suspected that it may 

to contain high-grade dysplasia (HGD), the medical term 

could indicate that the polyp 

A Plan and Budget Proposal for Fiscal Year 2005 

STORY OF DISCOVERY 

prostaglandin synthesis. Vane’s Nobel Prize winning discovery paved the way for future 

enzymes. At first, scientists knew of only one COX enzyme. In 1990, however, three 

Promising Therapies and Future Paths 

almost always progresses to cancer. Recent studies suggest that elevated levels of COX-2 

may contribute to the development of tumors originating at other sites in the body, including the breast, skin, lung, esophagus, bladder, cervix, head and neck, stomach, liver and 

More recently, three research teams found that daily intake of low doses of aspirin reduced 

cancer screening exams regularly. 

(non-cancerous) polyp in a 

67-year-old man's colon 

tumor arising from the epitheUnlike more common polyps, 

which are attached on a 

turn cancerous, it is removed 

surgically. In this case, after 

removal the polyp was found 

for cell abnormality, which 

was becoming cancerous. 
24 The Nation’s Investment in Cancer Research

A new era in biomedical research holds extraordinary potential for new strategies in cancer prevention, diagnosis, and treatment. Proteomics, specific biomarkers, and newer nanotechnology assays

will provide the basis for a wide range of technologies for early detection and diagnosis. Physicians

will have specific information on the stage of progression of most cancers, and patients will be treated with targeted agents both singly and in combinations uniquely designed to prevent some cancers

and control others with minimal or no side effects.

Targeted delivery of new drugs and real-time monitoring of drug levels through

biosensors will ensure ongoing treatment efficacy and minimize the possibility of

resistance. Cancer patients will more often experience a chronic rather than fatal

disease and will be able to enjoy a high quality of life. We will also be able to apply

our knowledge of the molecular signatures of cancer to predict the course of the

disease, individual responses to cancer/precancer therapies, and the risk of adverse

drug reactions for treating the most fatal cancers. Such approaches will allow for

the development and selection of more individualized and effective therapies.

PROGRESS IN PURSUIT OF OUR GOAL

An interdisciplinary, collaborative, cooperative approach is needed if we are to realize rapid, efficient translation of basic scientific advances into new tools, reagents,

and molecularly targeted lead compounds for use in clinical research. NCI is partnering with various groups as a way to carry out this research agenda. (See page 84.)

Identifying and Validating Molecular Targets for Cancer Intervention

Through the Molecular Target Drug Discovery (MTDD) program, investigators

are identifying novel molecular targets, validating these as targets for cancer therapy, and developing tests that determine how well potential agents work against

these targets. One researcher used a computational model to study the site of

interaction between a drug and a protein involved in apoptosis. Another team

discovered a breast cancer-relevant gene that is expressed differently in Caucasian

and African American patients. This discovery could help scientists to understand

differences among races in susceptibility to breast cancer. 

In the NCI Intramural Research Program, investigators are discovering new

hereditary cancer syndromes and identifying genes that contribute to disease,

such as the gene associated with clear cell renal carcinoma in von Hippel-Lindau

disease. The study of inherited mutations is providing new insight into sporadic

disease. In addition, the study of pathways for these inherited diseases may spur

new developments in future diagnostics and therapeutics.

The Chemical Genetics Institute (formerly the Molecular Targets Laboratory) was

first funded in Fiscal Year 2002 to capitalize on the opportunities emerging from

advances in genomics, molecular biology, combinatorial chemistry, informatics,

and imaging. Scientists are creating a resource of biological assays and chemical

probes (compounds used to study molecular targets) to study cancer-related 

Molecular Targets of Prevention, Diagnosis, and Treatment

Discovery 

The process of creating 

an effective, molecularly 

targeted cancer drug begins

with basic research and 

the search for chemical 

compounds with potential

anti-cancer properties and

molecules within cancer cells

and their surroundings that

might provide targets for 

cancer interventions. 
Through several NCI 

initiatives, chemists and 

biologists are collaborating 

to create libraries of 

compounds to be either 

evaluated for their overall 

therapeutic potential, or 

screened to identify those 

that modulate the biological 

activity of validated targets. 

Development 

targets. This work facilitates biological studies of cancer, including physiological 

and biochemical monitoring, and provides a platform for drug discovery. 

The Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative 

program designed to derive and characterize mouse models, and to generate 

resources, information, and innovative approaches to the application of mouse 

models in cancer research. Through the MMHCC, groups of academic 

researchers have created and are making available to other researchers mice with 

defined genetic alterations that predispose the animals to certain types of cancer. 

More than 75 strains were available as of 2003. These mouse models could serve 

as a basis for testing new, molecularly targeted treatment and prevention strategies. The Consortium will develop partnerships with pharmaceutical industry 

sponsors to facilitate the testing and evaluation of new compounds identified by 

Consortium members. (emice.nci.nih.gov) 

Identifying Compounds That Hit the Targets 

NCI provides, at no cost, samples of synthetic chemicals, collected natural products, and biological materials to investigators who want to screen them against 

molecular targets. 

•	 The National Cooperative Drug Discovery Groups (NCDDG) program supports innovative, interdisciplinary, multi-project approaches to discover new 

anti-cancer treatments. 

•	 In Biology and Chemistry Centers, multidisciplinary teams of scientists use a 

combination of chemical and biological techniques to create libraries of 

chemically-diverse structures with potential anti-cancer effects. Using 

“smart” assays, scientists screen the compounds to identify those that will 

interact with cancer-specific molecular targets. 

•	 The Rapid Access to NCI Discovery Resources (R*A*N*D) program expedites the development of drug research capabilities in academic institutions. 

R*A*N*D assists in the development of high-throughput laboratory assays 

to screen large numbers of promising chemicals. The program supports the 

development of libraries of chemicals for use by scientists. 

Providing Resources for Pre-Clinical Development of Promising Compounds 

The Rapid Access to Intervention Development (RAID) program provides preclinical 

drug development resources to academic institutions. One team is developing a 

steroidal compound that suppresses estrogen-stimulated breast tumor growth through 

inhibition of a particular enzyme. RAID is providing radiolabeled material as well as 

additional efficacy, formulation, and toxicology studies for this compound. Another 

researcher has hypothesized that a treatment regimen involving high-dose chemotherapy, stem cell transplantation, and an Yttrium-labeled antibody will prove effective for 

relapsed Hodgkin’s lymphoma. RAID is producing clinical-grade antibody that will 

be radiolabeled by the researchers. (dtp.nci.nih.gov/docs/raid/raid_index.html) 

The National Cancer Drug Development Group (DDG) supports the development of experimental cancer drugs for which NCI holds the FDA-approved 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 25 
Translating laboratory 

discoveries into agents 

for human use is an 

exacting task that requires 

very specific, interrelated 

activities. For example, 

investigators must produce 

sufficient quantities of a 

drug for formulation, 

stability, and safety testing. 

Subsequent studies enable 

scientists to determine the 

mode and amount of drug to 

use in early clinical testing or 

whether a drug should even 

be advanced to this stage. 

NCI is supporting this critical 

arm of drug development 

through a variety of initiatives. 

Investigational New Drug (IND) application, regardless of whether the drug was 

discovered by NCI, industry, academia, or another source. A number of promising agents from this program have progressed to clinical trials. One agent developed by DDG-supported researchers is a synthetic improvement on a naturallyoccurring anti-tumor antibiotic. This agent binds to DNA and is highly active in 

animal models against ovarian, melanoma, and breast tumors, while exhibiting 

less toxicity than the parent compound. Another agent developed through this 

program is a synthetic compound derived from a marine sponge that has shown 

anti-cancer activity in animal models representing breast and lung cancers, producing tumor-free animals in both cancers. (dtp.nci.nih.gov/docs/ddg/ddg_descript.html) 

The Interdisciplinary Research Teams for Molecular Target Assessment (IRTMTA) is a new program that enables interdisciplinary teams of scientists to develop 

molecular assays, molecular and cellular imaging probes, and other tools to assess 

the effects of targeted interventions in preclinical models and in early clinical 

trials. Groups are targeting angiogenesis, survival and proliferation signals 

for tumors, new ways to measure the effectiveness of tumor vaccines, and the 

structure of tumor chromosomes. 

The Flexible System to Advance Innovative Research (FLAIR) provides funds to 

small businesses to develop cancer therapeutic and prevention agents. FLAIR 

supports the development of novel drug delivery systems, imaging technologies, 

anti-angiogenesis drugs, and anti-metastatic agents; the design of small compounds 

able to mimic the action of proteins; and agents that sensitize cancer cells to radiation. 

Within the Intramural Program, the Molecular Targets Development Program 

(MTDP) facilitates the discovery of compounds that may serve as bioprobes for 

functional genomics, proteomics, and molecular target validation research. During 

the past year, the MTDP has focused on biomolecular assay development, drug development, and collaborations with various academic and private pharmaceutical partners. 

Developing New Strategies for Cancer Intervention 

Intramural laboratories are currently developing treatment and prevention therapies for a variety of cancers. Integration of molecular imaging, molecular signatures, and molecular therapeutics with radiation therapy is a high priority of 

NCI’s Intramural Program because new anti-cancer agents may ultimately be used 

in combination with radiation therapy. The Radiation Modifier Evaluation 

Module (RAMEM) program will serve individual investigators and industry in 

the design and development of treatment programs for the use of novel molecular, 

biologic, and cytotoxic agents in conjunction with radiation therapy. Intramural 

investigators have also shown that “adoptive transfer” is a promising approach 

to treating patients with refractory metastatic melanoma and has potential applications to other tumor types. Cells of the immune system are harvested from the 

patient, activated against the tumor antigen, and re-introduced into the patient, 

where they attack the tumor. 

26 The Nation’s Investment in Cancer Research 
Delivery 

Once preclinical testing has 

been completed, agents 

that are deemed suitable 

for human testing enter 

early-stage clinical trials 

for safety and efficacy. 

Compounds that survive 

early clinical testing proceed 

to broader clinical testing to 

determine whether cancer 

patients or those at risk for 

cancer will actually benefit 

from the agents. 

Moving Developed Agents into Clinical Testing for Safety and Efficacy 

The RAID and DDG programs have delivered more than 30 new therapies for 

clinical testing in the past 10 years. 

•	 One therapy that uses a virus modified to deliver a pair of therapeutic suicide 

genes to prostate tumors entered clinical trials in January 2002. NCI produced the virus, conducted in vivo studies, and assessed initial safety studies. 

•	 Clinical trials have been initiated in the United States and England on a derivative of geldanamycin, a potent growth inhibitor of several pediatric neural 

tumor cell lines. NCI contractors produced a large quantity of geldanamycin 

and developed a viable formulation of the derivatives for clinical use. 

•	 An immunotoxin (BL-22) developed intramurally and manufactured by NCI 

is being tested in patients with hairy cell leukemia (HCL) and investigators are 

modifying it for testing in patients with chronic lymphocytic leukemia. 

•	 Another compound, a histone deacetylase (HDAC) inhibitor, is being used for 

cytotoxic T-cell lymphoma therapy. 

The Rapid Access to Prevention Intervention Development Program (RAPID) 

supports the movement of agents for cancer prevention into clinical testing. 

RAPID helps academic investigators expedite preclinical and early clinical drug 

development of investigational agents with the potential to prevent, reverse, or 

delay carcinogenesis. Current projects include a second-generation human 

papillomavirus (HPV) vaccine that is both economical and stable; mycochemicals with specific efficacy in lung and colon cancer prevention models; and 

modified components of dietary crucifers developed in preclinical prevention 

models of breast and prostate cancer, as well as HPV replication models. 

(www3.cancer.gov/prevention/rapid) 

Supporting Clinical Trials of Molecularly Targeted Agents for Cancer Prevention 

NCI supports clinical trials for chemoprevention that measure or identify molecular 

targets involved in the cancer process. 

•	 The Selenium and Vitamin E Cancer Prevention Trial (SELECT) will assess 

the molecular genetics of cancer risk and associations between diet and 

prostate cancer. 

•	 Investigators are studying the estrogen receptor as a key to breast cancer risk 

in the Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen 

and Raloxifene (STAR). NCI has also begun an initiative that funds investigator-initiated research focused on two key aspects of this problem: validating surrogate biomarkers and identifying potential molecular targets for 

chemoprevention of human ER-negative breast cancer. 

•	 Epidemiologic studies have suggested that prostate cancer risk may be higher in 

men who consume only small amounts of fruits and vegetables or high amounts 

of milk, dairy products, and meat. NCI is fostering investigator-initiated research 

to identify and characterize molecular targets affected by nutrients, and further, to 

determine how these targets can affect outcomes in prostate cancer prevention. 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 27 
MOLECULAR TARGETS OF PREVENTION, DIAGNOSIS, AND TREATMENT 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Facilitate the expand- Discovery 

ed exploration of the 1. Identify, characterize, and validate the combinations of deregulated cellular 

causes of cancer and proteins and pathways that cause cancer, in order to find targets for treatment 

the discovery, devel- and prevention. $18.75 M

opment, and delivery ■ Expand research to identify cellular targets, discover related anti-cancer agents, and quickly transof agents that specifi- late these new discoveries for use in clinical trials through the Academic Public Private Partnership 

cally “target” these Program (AP4) and other grant mechanisms. Provide late drug development assistance. $4.75 M 

causes to prevent, ■ Identify cellular targets and screen potential cancer preventive agents using human cells from indidiagnose, treat, and viduals with autosomal dominant cancer syndromes through genomic, proteomic, and bioinformatprovide follow-up ics approaches. $5.00 M 

surveillance of cancer. ■ Expand the availability of NCI discovery resources to academic laboratories for small molecule and 

biologics through the Rapid Access to NCI Discovery Resources (R*A*N*D) program. $1.00 M 

■ Accelerate the pace at which accurate, reproducible mouse models of human cancers are made 

available, and define the process of using mouse models to evaluate targeted therapeutics, through 

support of the Mouse Models of Human Cancers Consortium. $2.00 M 

■ Identify and evaluate agents to prevent or ameliorate cancer-causing radiological injury due to 

terrorist acts. $5.00 M 

■ Support an intramural Molecular Targets Discovery Program. $1.00 M 

Development 

2.	 Provide the infrastructure for researchers to find effective interventions directed at validated targets (e.g., assays, proteomics, imaging). $16.00 M 

■ Expand the number of new drug candidates arising from the National Cooperative Drug Discovery 

Groups (NCDDG), through the Drug Development Group (DDG), and Rapid Access to Intervention 

Development (RAID) programs. $1.00 M 

■ Develop a translational research program to closely link molecular imaging, cancer signatures, and 

molecular targets. The ability to conduct multiple studies will provide a robust data set to understand 

the biology behind the image needed to credential new molecular targets. $3.00 M 

Supporting Clinical Trials of Anti-Cancer Vaccines 

NCI has initiated a consortium to develop a new generation of anti-cancer vaccines. 

This consortium consists of translational research laboratories within the Intramural 

Program, expert clinicians from numerous institutions throughout the country, and 

representatives from the biotechnology and pharmaceutical industries. 

NCI Clinical Center researchers have initiated two clinical trials examining a vaccine that 

activates cytotoxic (killer) T-cells to attack tumor cells in patients with advanced colorectal, pancreatic, and lung carcinomas. Another group is conducting a similar trial for 

prostate cancer patients. In a Phase III randomized trial, investigators are testing an indi28 The Nation’s Investment in Cancer Research 
■ Promote the early assessment of molecular targets in clinical trials and the discovery of drugs for 

potential combination trials through increased support for the Interdisciplinary Research Teams for 

Molecular Target Assessment (IRTMTA). $2.00 M 

■ Accelerate intervention development through expanded support for the Rapid Access to 

Intervention Development (RAID) program. $3.00 M 

■ Evaluate the effects of dietary and pharmaceutical anti-oxidants and anti-inflammatories on the 

effectiveness of radiation therapy. $3.00 M 

■ Develop a clinical proteomics initiative, with supporting bioinformatics, to use patient biopsies to 

develop new laboratory tools for clinical proteomic applications in human cancer and drug toxicity 

detection. This resource would be available to cooperative groups to provide data or use the data 

generated. $2.00 M 

■ Support an intramural Molecular Targets Development Program. $2.00 M 

3. Facilitate the steps necessary to develop therapies using targeted clinical 

agents alone or in novel combinations with radiation therapy. $11.50 M 

■ Accelerate the movement of agents from the laboratory through clinical trials for efficacy by increasing funding to the Rapid Access to Preventive Intervention Development (RAPID) program. $1.00 M 

■ Expand development of novel methods of drug formulation and drug delivery through new Small 

Business Innovation Research (SBIR) initiatives. $2.00 M 

■ Expand assistance to small business drug research and development through the Flexible System 

to Advance Innovative Research (FLAIR) program. $3.00 M 

■ Increase support to individual investigators and industry for the development of treatment programs 

using new agents with radiation therapy. Collaborate with industry and individual investigators to 

establish a system for alerting clinical investigators when agents are ready for clinical trials. $0.50 M 

■ Provide infrastructure support to Cancer Centers and other research institutions for staff and facilities dedicated to clinical cancer prevention research. $5.00 M 

Management and Support 	 $ 1.40 M 

Total $47.65 M 

vidualized vaccine against B-cell follicular lymphoma. This trial is being conducted 

through an arrangement with a biotechnology investment group. 

Intramural laboratories have been collaborating on early-phase clinical trials of prophylactic HPV-16 vaccine in unaffected volunteers for the prevention of cervical cancer. 

The vaccine has been found to be safe while producing an immune response. NCI and a 

pharmaceutical partner will conduct a large-scale trial in Costa Rica. Another intramural laboratory is developing new targeted approaches to replace standard, cytotoxic 

chemotherapy for the AIDS-related malignancy Kaposi’s sarcoma. 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 29 
Quality Patient Care Includes Radiation Oncology 

That Is Crosscutting and Multidisciplinary 

Radiation oncologists are providing care for increasing numbers of cancer patients at some point during the course 

of their disease. Radiation is used both alone and in combination with other modes of therapy. For example: 

• Radiation oncology is at the forefront of image-guided therapy. Beam-shaping techniques such as 3D-conformal therapy and intensity-modulated radiation therapy 

(IMRT) allow health care providers to administer higher doses of radiation to the 

tumor while exposing normal tissue to reduced amounts. 

•	 Technological advances in brachytherapy permit radiation sources to be placed 

within certain tumors. 

•	 Proton particle beam therapy allows more precise administration of radiation to 

cancerous tissue. 

Proton radiation therapy • Radioimmunotherapy involves the use of radioactive molecules attached to mono- is used to treat melanoma clonal antibodies to attack cancer cells throughout the body. cancer of the choroidea, • Combination radiation and chemotherapy permits organ-sparing curative treat- the middle layer of the ment and has increased patient survival rates for a number of diseases, compared vertebrate eye, between the to using either type of therapy alone. retina and sclera. • New molecularly targeted anti-cancer drugs are often more effective when administered in combination with radiation therapy. Basic and clinical researchers are 

studying cancer-related molecular pathways to design improved chemo-radiation 

approaches. 

NCI places a high priority on crosscutting research into 

new radiation technologies. 

NCI’s intramural researchers collaborate with universities and industry, linking studies 

in molecular imaging, molecular biology, and molecularly targeted therapy. This multidisciplinary research is helping oncologists to understand molecular processes affected by radiation, improve tumor control, and lessen injury of normal tissue. Research in 

normal tissue radiation toxicity will also help the Nation to prevent and/or treat possible injury from radiological or nuclear terrorism. 

Beyond intervention development, NCI has been a leader in radiation oncology quality assurance, pioneering the Patterns of Care studies over three decades ago to investigate adoption of recommended treatments for the most common cancers. (See page 

52.) NCI is now implementing shared quality assurance programs that will improve 

the technological sophistication of radiation oncology, worldwide, and create data 

sharing abilities via telemedicine. This improvement in technological resources is the 

backbone of the new cancer disparities research partnership program,1 designed to 

enable research at institutions that primarily serve low-income, underserved, and ethnic and minority populations. (See also page 59.) NCI’s radiation oncology research 

embraces the goal of ensuring that highly effective cancer interventions are accessible 

to all who need them. 

1

Supported through the Cooperative Planning Grant for Cancer Disparities Research. 

30 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 31

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS

Cancer care is critically dependent on imaging technologies, which are used to detect tumors early, 

when they are easier to treat, and to guide therapy or surgery. As our knowledge of the molecular 

basis of cancer increases, so does the need for imaging methods that provide clinicians with telling

details about the molecular environs of patients’ tissues. We must also focus resources on the imaging

of precancerous conditions so that more cancers can be diagnosed and treated before there is any 

evidence of anatomic change. 

Investment in cancer imaging technologies is pivotal to achieving NCI’s challenge

goal of eliminating the suffering and death due to cancer. Oncologic imaging guided intervention (OIGI), for example, is a rapidly evolving area of interest that may

be used not only to cure some cancers and precancerous lesions, but in many more

cases to provide minimally invasive, well-tolerated palliative therapies. This latter,

easily achievable objective will help transform certain cancers from debilitating and

deadly illnesses into chronic, well managed diseases that have little or no adverse

effect on the daily lives or life expectancies of patients. 

To ensure the speedy movement of lifesaving new cancer interventions to patient

care, NCI must also invest in imaging and molecular sensing techniques that help

the preclinical researcher. For example, micro-imaging technologies will permit

researchers fuller use of the increasing number of mouse models of human cancer

to uncover the genetic basis of specific tumors and examine response to experimental therapies. The development of functional imaging methods for mouse models and molecular biosensors for use in animal models will help determine how

newly discovered defects in genes and proteins interact to cause cancer. 

As scientists make exponential progress in understanding the molecular basis of

cancer, this is an opportune time for NCI to invest in cancer imaging and molecular sensing technologies that will increasingly save and improve lives.

PROGRESS IN PURSUIT OF OUR GOAL

Discovering Better Imaging Technologies and Techniques

NCI has played a major role in fostering functional imaging through initiatives such

as In Vivo Cellular and Molecular Imaging Centers (ICMICs). Each ICMIC brings

together experts from diverse scientific and technological backgrounds to conduct

multidisciplinary research on cellular and molecular imaging in cancer. Seven

ICMICs operate nationwide, including two new centers established in 2003. At one

of the new centers, researchers will use their expertise in magnetic resonance (MR),

positron emission tomography (PET), and optical imaging to understand cancer vascularization, invasion, and metastasis — knowledge that can be applied to achieving

effective cancer therapies. Scientists at the second new center will apply their radiochemistry expertise, integrated with molecular and biochemical techniques, to design

and generate new molecularly targeted cancer agents. The Small Animal Imaging

Resource Programs (SAIRPs) at 10 centers around the country increase the efficiency, synergy, and innovation of small-animal imaging research. Launched in 1999,

Cancer Imaging and Molecular Sensing

Discovery 

Computed tomography and

magnetic resonance imaging

permit remarkable accuracy

in detecting whether a tumor

has invaded vital tissue,

grown around blood vessels,

or spread to distant organs.

Molecular or “functional”

imaging is increasingly used

in place of patient biopsy.

Imaging guided interventions

allow precise delivery of

tumor-destroying approaches (e.g., chemicals and radiation) minimizing trauma and

damage to healthy tissue,

shortening recovery times,

and reducing healthcare costs. 
As small animal imaging 

becomes an increasingly 

valuable tool in cancer 

research, NCI seeks to 

optimize its availability 

to investigators. 

SAIRPs make the necessary equipment and personnel available to investigators, 

improve and enhance technologies and techniques for imaging small animals, and 

foster cross-disciplinary collaborations. For example, SAIRP researchers have established research techniques for imaging apoptosis in tumors in real-time; imaging 

elusive protein-protein interactions; tracking lymphocytes involved in immunotherapy approaches; and monitoring the response of tumors to experimental therapies. 

Collaborations between SAIRPs and other animal research groups allow 

researchers to study in vivo, molecular intricacies of cancer development not otherwise observable. An Imaging Working Group is enhancing collaborations between 

SAIRPs and the Mouse Models of Human Cancers Consortium (MMHCC). 

In a separate effort, launched in 2003, NCI is increasing researcher access to 

small-animal imaging equipment by providing funds for purchasing or upgrading 

equipment to NCI-funded small-animal imaging researchers with a history of 

collaborating with other investigators. The recipients will share the equipment and 

provide imaging expertise to a number of other NCI-funded researchers. 

a tissue sample to allow study of the almost instantaneous interactions occurring 

in vivo biosensors to 

detect molecular targets of cancer: 

in vivo; 

ICMIC Scientists 

Develop a Biosensor to 

Permit Imaging of 

Molecular Interactions 

Cancer researchers seek to understand how interactions among molecules such as 

genes and proteins sometimes go awry, transforming a normal cell into a cancer cell. 

Laboratory scientists routinely design and use biosensors that interact chemically with 

among such molecules. These assays often require investigators to carefully isolate 

and prepare from the biological sample the type of molecules they want to study — a costly, time-consuming process 

that uses up quantities of precious sample. 

Recently scientists supported by NCI’s In Vivo Cellular and Molecular Imaging Centers (ICMICs) created a biosensor 

that allows researchers to slow down the activity of molecules so that their interactions can be imaged, rather than 

studied by chemical assay. These biosensors contain magnetic relaxation switches (MRSs), tiny probes made up of 

nanoparticles with magnetic properties that will slow down, or “relax,” the activity of nearby molecules enough for their 

activity to be captured by magnetic resonance imagery or nuclear magnetic resonance imagery. The MRS biosensors 

worked well regardless of sample turbidity, variations in temperatures, or solution type — permitting researchers to 

use MRSs without costly sample preparation. ICMIC investigators also demonstrated that MRSs work well in a 

high-throughput assay format. Furthermore, several features of MRSs highlight their potential as 

materials used to make the probes have little or no toxicity; the necessary imaging techniques are commonly used and magnetic nanoparticles can be modified to be internalized by cells. 

With further development of MRSs and accompanying imaging systems, this ICMIC advance should have broad biomedical applications, including widespread use by investigators developing molecularly targeted cancer interventions. 

32 The Nation’s Investment in Cancer Research 
Development 

Following preclinical testing, 

new cancer imaging technologies and techniques 

are often evaluated through 

one of NCI’s clinical trials 

cooperative groups. These 

groups are networks of 

health care professionals 

affiliated with medical 

schools, teaching hospitals, 

and community-based 

cancer treatment centers. 

Developing Promising Imaging Advances 

NCI realizes that the discovery of new imaging agents will have limited clinical 

impact without the resources to help move promising agents through the development phase. Researchers often lack the resources to conduct preclinical testing (e.g., 

tests for safety, pharmacology, toxicology, etc.). These data must be submitted to the 

Food and Drug Administration (FDA) in an Investigational New Drug (IND) application before the agent can be tested in humans. NCI’s Development of Clinical 

Imaging Drugs and Enhancers (DCIDE) program fills this gap by providing, on a 

competitive contract basis, NCI resources to perform this preclinical testing. A relatively new program, DCIDE has already reviewed 15 compounds, has completed 

preclinical evaluation for one agent, and has three others in various stages of synthesis and testing. DCIDE resources also permit NCI to file INDs for agents that 

have withstood preclinical testing and are highly promising, but for which an IND 

has not yet been filed. Currently, INDs for two such agents are in progress and two 

others are under consideration. 

In another effort to shorten the time it takes to move a promising new agent from 

discovery to clinical testing, NCI recently developed a contract program to validate 

imaging methodologies for preclinical testing of new drugs. Through this program, 

scientists have developed a variety of methods for using dynamic contrast-enhanced 

magnetic resonance imaging (MRI) and MRI blood-volume measurement to visualize 

the effects of anti-angiogenic agents in animal models. In 2003, researchers applied 

these new techniques to preclinical testing of several therapeutic anti-angiogenic 

agents. Researchers have now begun examining PET in a similar manner for use in 

assessment of blood flow, blood volume, and metabolism in preclinical drug studies. 

The American College of Radiology Imaging Network (ACRIN), supported by 

NCI, is conducting the Digital Mammography Imaging Screening Trial (DMST). 

This large-scale effort is comparing the diagnostic power of digital mammography 

to conventional, film-based mammography. More than 32,000 women have 

enrolled in DMST at 31 sites across the United States and Canada. In another largescale trial, ACRIN and NCI collaboratively launched the National Lung Screening 

Trial (NLST) in September 2002. This 8-year study conducted at 30 sites nationwide will determine whether lung cancer screening using low-dose spiral computed 

tomography in high-risk populations reduces mortality from this disease compared 

with standard x-ray screening. NLST scientists will also assess the stage of tumors 

when first detected, quality-of-life and psychological issues for people who test positive for lung cancer, economic consequences, and other potential differences 

between the two screening methods. NLST researchers have enrolled over 21,000 

of the 50,000 smokers and former smokers1 needed to conduct this study. 

1 Participants must be between the ages of 55-74 with a current or previous smoking history of at least 30 pack-years; 

former smokers must have quit within the preceding 15 years. 

A Plan and Budget Proposal for Fiscal Year 2005 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

33 
CANCER IMAGING AND MOLECULAR SENSING 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Accelerate discovery 1. Expand the discovery and development of novel imaging agents, devices, and 

and development of methods for cancer. $15.00 M 

imaging methods, ■ Foster multidisciplinary research through support of In Vivo Cellular and Molecular Imaging Centers 

biosensors, and mini- (ICMICs). 

mally invasive image- ■ Increase the number of imaging agents supported by the Development of Clinical Imaging Drugs 

guided interventions and Enhancers program from three to five per year. $2.00 M 

for cancer and pre-

■ Increase collaborations between Small Animal Imaging Resource Programs (SAIRPs) and other NCI cancerous conditions. programs, such as the Mouse Models of Human Cancers Consortium. $2.00 M 

■ Establish a repository of imaging agents, available to investigators, at NCI-Frederick. $2.00 M 

■ Establish a research resource of databanks of standardized digital image or spectroscopy data 

associated with known clinical outcomes. $3.00 M 

■ Expand the NCI-funded, publicly available Molecular Imaging Database of imaging agents. $1.00 M 

■ Expand the Network for Translational Research in Optical Imaging (NTROI). $3.00 M 

■ Support an intramural Molecular Imaging Program (MIP) to develop novel imaging biosensors and 

techniques. $2.00 M 

2. Integrate advanced imaging methods into therapeutic clinical trials. $14.00 M 

■ Support correlative imaging studies, such as monitoring response to therapy, with supplements to 

Clinical Trials Cooperative Groups. $4.00 M 

■ Increase the contract support for early clinical trials of imaging agents. $2.00 M 

■ Develop imaging cores within NCI-funded Cancer Centers. $4.00 M 

In other efforts, ACRIN and partners are studying: 

•	 Whether contrast-enhanced breast MRI can be used as a biomarker that can predict 

patient outcome and guide individualized treatment — in partnership with the NCIsponsored cooperative group, Cancer and Leukemia Group B, and NCI breast cancer 

Specialized Programs of Research Excellence (SPORE). 

•	 The potential role that breast ultrasound, using standardized technique and interpretation criteria, should play in screening women at high risk for breast cancer — in partnership with the Avon Foundation. 

•	 Whether PET measurement of changes in tumor volume in non-small cell lung cancer 

patients, before and after treatment, can help predict long-term patient outcome. 

•	 Whether whole body MRI and FDG2

-PET are valuable for detecting metastatic disease 

in common primary tumors in children. 

•	 Whether combined MR/magnetic resonance spectroscopic (MRS) imaging performs better 

than MR imaging alone for localizing prostate tumors prior to radical prostatectomy. 

2 FDG-PET utilizes the radioisotope 18F-2-fluoro-2-deoxy-D-glucose. 

34 The Nation’s Investment in Cancer Research 
■ Validate imaging methodologies in preclinical testing of new drugs through an expanded contract 

program. $1.00 M 

■ Support an intramural Radiation Oncology Molecular Assessment and Technology Program 

(ROMAT) integrating multiple imaging approaches in clinical studies. $3.00 M 

3. Accelerate the development and clinical testing of image-guided interventions 

(IGI). $11.25 M 

■ Develop an IGI Animal Laboratory Network. $2.25 M 

■ Develop an IGI Clinical Centers of Excellence Program. $6.00 M 

■ Establish an Imaging-Guided Oncologic Trials Network. $3.00 M 

4. Stimulate research on components and systems integration of devices for 

in vivo molecular sensing (biosensors). $4.00 M 

■ Develop biosensors or components of biosensors for in vivo use by funding supplements to investigators in the Innovative Molecular Analysis Technology Program and the Unconventional Innovation 

Program. $2.00 M 

■ Fund a Center for Biosensors in Oncology, based on the National Science Foundation Engineering 

Research Center model. $2.00 M 

Management and Support 	 $ 0.50 M 

Total $44.75 M 

NCI is also supporting a large project to assess the emerging technologies of fluorescence and 

reflectance imaging spectroscopy for diagnosing cervical cancer. (See page 74.) 

Advancing In Vivo Biosensor Research 

Investigators in the Unconventional Innovations Program (UIP) and the Fundamental 

Technologies for Biomolecular Sensors (FTBS) Program are developing molecular biosensors that can be either injected into the bloodstream or taken orally, for the purpose of 

detecting and destroying cancer cells. These biosensors are multifunctional nanoparticles 

that range in size from 10 to 250 nanometers in diameter (a typical human hair is about 

50,000 nanometers wide). To build a molecular biosensor, researchers first construct a base 

particle to which they attach ligands, such as peptides or monoclonal antibodies that recognize and bind to cells that overexpress specific cancer-related proteins (e.g., PSA, Her-2). 

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS 

A Plan and Budget Proposal for Fiscal Year 2005 35 
Delivery 

Once attached to the cancerous cell, a contrast enhancing agent that is also carried 

by the biosensor is used to obtain a high quality image. The particle then releases a 

therapeutic compound to kill the cell. To date, several of the participating researchers 

have synthesized and characterized suitable base particles and have developed the 

chemistry needed to attach ligands, contrast enhancement agents, and therapeutics. 

They have performed in vitro and in vivo testing for binding, image contrast, 

therapeutic delivery, and cell killing. Many of the researchers are now scaling up 

production of the biosensors for larger testing, and are in some cases actively pursuing clinical trials at various Cancer Centers. 

Delivering Imaging Advances to Patient Care 

NCI is supporting partnerships to accelerate commercialization of tested new technologies to help move them into mainstream clinical use. In 2003 NCI initiated a 

program to build academic/industry partnerships to ensure development of promising cancer-specific biomedical imaging systems and methods. Using seed grants, this 

program supports large and small companies in their efforts to optimize imaging 

devices and agents developed on a small scale, but with promise for production on 

a commercial scale. These companies might, for example, integrate informatics 

platforms into imaging systems, adapt systems to perform specialized molecular 

imaging, refine software developed by lay researchers, or develop and validate 

“orphan” imaging technologies. 

One NCI-funded research team, in collaboration with Advanced Magnetics, Inc., 

has developed a non-invasive imaging technique that appears to be superior to 

existing clinical methods for staging prostate cancer. This new investigational procedure is used to evaluate an important staging criterion: whether, and to what 

extent, malignant cells have reached surrounding lymph nodes. Investigators 

employ contrast-enhanced MRI, which uses a contrast agent to make lymph nodes ® in the imaged area appear bright. The procedure also uses the compound Combidex, 

which is composed of nanoparticles that attach only to cells in normal lymph nodes 

and are unable to attach to malignant cells. Combidex® causes the normal lymph 

nodes to appear dark on an MRI, while malignant cells in affected lymph nodes 

remain bright and are easily located. FDA expects to release this new 

technique soon for clinical use. Other potential applications include the staging of 

cancers of the breast, bladder, head and neck, and cervix. 

36 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 37

BROAD RESEARCH PRIORITIES: CORE SCIENTIFIC AREAS

Cancer Advocates Help Put a

Human Face on Cancer Research

You remind us why we are here.

“I was invited to be the patient representative on an NCI peer review panel for a proposed clinical trial.

The other members of the panel were well respected scientists who focused with diligence and purpose

on the scientific merit of the clinical trial. I, by raising issues related only to the patients, sharpened that

focus. As one scientist said, ‘You remind us why we are here.’” — Cancer Advocate 

Cancer advocates may be cancer survivors, family members or life partners, or 

people integrally involved in cancer-related activities, such as support group leaders

or hotline workers. They come from diverse age groups, races, ethnicities, educational levels, and geographic locations. Cancer advocates are intimately familiar with

the hopes, struggles, joys, losses, and successes of cancer patients, those at risk for

cancer, and their loved ones. Their advocacy helps present the human face of cancer

to scientists, administrators, and the general public, reminding us of the “why” in

cancer research.

NCI draws upon the expertise of cancer advocates through two major vehicles. The

Director’s Consumer Liaison Group (DCLG)1 is made up of 15 cancer advocates,

each representing a unique constituency in the advocacy community. DCLG members advise the Director of NCI on a wide variety of issues, programs, and research

priorities. The Consumer Advocates in Research and Related Activities (CARRA)2

links cancer advocates with opportunities to help NCI, for example through 

participation in the peer review process for research proposals; participation on

Progress Review Groups; and review of patient-oriented materials for readability

and relevance.

NCI is highly dependent on cancer advocates and the perspectives they bring to all

aspects of the cancer research planning process, and cancer advocates are impacting

NCI’s research efforts. For example, recent advocacy efforts have contributed to:

• Expanded research focus on quality of cancer care, quality of life for cancer

patients and survivors, and cancer health disparities

• A more streamlined clinical trials process designed to move promising agents to

the market earlier

• An improved informed consent process for clinical trials that helps patients 

better understand the potential risks and benefits of participation

• More consistent use of plain language in NCI consumer publications and 

Web sites

• Better public understanding of the importance of, and NCI’s role in, cancer

research. 

1 For more information on DCLG, go to deainfo.nci.nih.gov/ADVISORY/dclg/dclg.htm. 2 For more information on CARRA, go to la.cancer.gov/carra.
38 The Nation’s Investment in Cancer Research

Much is known and documented about the harmful effects of tobacco. Tobacco use is the leading preventable cause of illness and death in the United States. Cigarette smoking is the primary reason people die from lung cancer, coronary heart disease, chronic obstructive pulmonary disease, and stroke.

Cancers of the lung, oral cavity, pharynx, larynx, esophagus, pancreas, urinary bladder, and renal

pelvis all have been scientifically linked to tobacco use. More recent research connects tobacco use

to still more cancers. A 2002 International Agency for Research on Cancer (IARC) monograph established a causal association between cigarette smoking and cancers of the nasal cavities and nasal

sinuses, stomach, liver, kidney, and cervix, as well as myeloid leukemia. Why then do people choose

to begin and continue smoking in spite of these health risks? This is the challenge for NCI and other

research organizations and institutions as we work to reduce tobacco’s staggering burden on our

Nation’s health. 

Of the many obstacles that confront the research community in the fight against

tobacco-related disease, two are particularly complex: (1) the addicting nature of

tobacco products, and (2) the impact of tobacco advertising and marketing. These

factors drive the continued use of tobacco products even when the users are fully

aware of their increased risk of disease and premature death. Adolescents are particularly vulnerable; almost 90 percent of adult current smokers began smoking before

the age of 18. At this age, individuals tend to be less than fully aware of the risks and

their implications and less able to make an informed, educated decision independent

of external influences. Therefore, research on preventing youth smoking must focus

on increasing young people’s awareness of the harmful consequences of tobacco use

and addiction; deflecting the presence of tobacco industry advertising messages; and

decreasing the acceptability of tobacco use in physical and social environments.

Equally important is the role of genetics and its interaction with psychosocial and

environmental factors in the development or onset of tobacco dependence.

Clearly, NCI cannot achieve its Challenge Goal to eliminate suffering and death

due to cancer without dramatically reducing and treating tobacco use and tobacco-related cancers across all ages and populations. This requires an integrated,

multidisciplinary approach to decipher the interplay of social, psychological,

behavioral, environmental, and biological/genetic determinants of tobacco use

and tobacco-related cancers. Because many tobacco-related cancers take years to

develop, making investments consistent with the enormous burden of tobaccorelated disease now will lead to substantial benefits in the future.

PROGRESS IN PURSUIT OF OUR GOAL

The intransigence of tobacco use and its disease consequences, along with its complex, multidimensional determinants, led the scientific community to recognize the

need for new research models and paradigms that are integrated across disciplines.

Transdisciplinary research, a process by which researchers work jointly, using a

shared conceptual framework that draws together discipline-specific theories, concepts,

Research on Tobacco and Tobacco-Related Cancers

Discovery

• Approximately 440,000

deaths per year in the

United States are 

caused by tobacco use.

• Worldwide, more than 

3 million people die 

every year because of

tobacco use.

• Approximately 46.5 million

American adults, or 23.3

percent of the population,

are current smokers;

approximately 44.3 million

adults, or 22.2 percent of

the population, are former

smokers. 

• Approximately 28.5 percent

of high school students

identified themselves as

smokers in 2001.

• In the United States, almost

one-third of the approximately 750,000 youth who

become regular smokers

each year will ultimately die

as a result of a smokingrelated illness.
Collaborative TTURC projects 

include: 

• 	 Development of a measure 

for nicotine dependence 

• 	 Joint studies related to 

genetic/cultural/environmental interactions in 

tobacco use 

• 	 Studies of the interrelationship of culture, mood, and 

smoking 

• 	 Adolescent studies investigating the influence of peer 

interaction, depression, 

and hostility on smoking 

initiation and maintenance 

• 	 Genetic studies of treatment 

response 

and approaches to address common problems, was identified as the most promising approach to accelerate discovery. In 1999, NCI, the National Institute on Drug 

Abuse (NIDA), and the Robert Wood Johnson Foundation jointly funded 

Transdisciplinary Tobacco Use Research Centers (TTURCs) within seven academic 

institutions. As of 2003, over 100 researchers involved in nearly 100 major research 

projects, pilot projects, and cores (e.g., training, biostatistics, administrative and 

transdisciplinary) are involved in research at these seven centers. 

At one TTURC, investigators generated the first empirical evidence that the 

CYP2B6 gene may influence the effectiveness of treatment with buproprion. This 

research team, composed of scientists who study behavior, neuroscience, pharmacology, and genetics, gained insight into specific neuronal and pharmacological 

mechanisms that may explain genetic effects on individual response to smoking 

cessation treatment. In clinical testing at another TTURC, researchers developed a 

single-photon emission computed tomography (SPECT) radiotracer for imaging 

certain nicotine acetylcholine receptors in the brain. This breakthrough will open 

new directions for cross-disciplinary research on receptor response during smoking 

and smoking cessation, while considering the effects of environmental, emotional, 

and behavioral factors. TTURC-supported research revealed links between attention deficit hyperactivity disorder (ADHD) and susceptibility to tobacco industry 

marketing among adolescents. Based on findings that nicotine increases dopamine 

levels in animal and preliminary clinical studies, one TTURC sponsored a study of 

selegiline (an MAO-B inhibitor that inhibits dopamine metabolism) as a treatment 

for tobacco addiction. In an early trial, selegiline was superior to placebo for 

smoking cessation. 

Supporting Clinical and Population Studies on Smoking and Cancer 

Longitudinal, screening, and cohort studies that involve genetic and biomarker 

components from tissue, blood, urine, sputum, and other bodily fluids are providing new information about the interplay among one’s cancer risk and tobacco and 

other exposures such as alcohol, diet, occupation, and radon. For example, one of 

the largest molecular epidemiology studies of lung cancer in the world, a multicenter case-control study of lung cancer and tobacco use, is under way in Milan, 

Italy. This trial includes collection of extensive questionnaire and biospecimen data, 

and is unique in collecting information on many other factors, including tumor 

tissue obtained in surgery, demographics, tobacco use, alcohol use, occupational 

exposures, diet, and medical illness. Investigators will apply advanced technologies 

to explore protein and expression patterns and the genomic correlates of lung 

cancer and tobacco use. 

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), the 

Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC), and the 

Shanghai Women’s Study are all large cohort studies that include biospecimens and 

questionnaire data with a focus on tobacco-related cancers. Two studies using highthroughput genotyping are planned within the PLCO to examine genes involved in 

“ever” and current smokers and explore the relationship of genes to emphysema 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 39 
Smoking Raises the Risk of Many Cancers 

Tobacco-Related Cancers in Women – 

I started smoking when For every woman who smoked in 1950, 600 women smoke today. And as more women smoke, 

I was 16 and quit in more suffer and die from smoking related disease. Many American women are unaware of just 

my early 30s. I was how dangerous smoking can be. Here are the facts: 

shocked when the • Lung cancer has now replaced breast cancer as the number one cancer killer of women. 

doctor told me that my • Tobacco use is a major cause of cancers of the bladder, mouth, larynx, and esophagus. 

bladder cancer may • Tobacco use is a contributing cause of cervical cancer, myeloid leukemia, and kidney, 

well have been caused colon, stomach, and pancreatic cancers. 

by smoking. So far it’s • Nearly 20 million women have successfully quit smoking but remain at risk for many cancers. 

cost me the misery of 

four surgeries and the NCI-supported research has shown that 14 percent of Hispanic women and 22 percent of 

loss of my bladder. White women smoke. Smoking rates are higher yet among African American women (about 24 

If only I had known . . . percent) and much higher among Native American and Alaskan Native women (about 35 percent). 

Poor and less educated women are more likely to smoke. A better grasp of the underlying causes of these disparities is critical to developing effective interventions to help all women. 

Tobacco industry marketing frequently targets young and minority women, and studies have 

revealed the effectiveness of this technique, especially for youths. Most women smokers 

begin as teenagers, before high school graduation. Of the millions of women who try to quit 

smoking each year, only a small percentage succeed. African American, Hispanic, younger, 

and less educated women have the lowest quit rates. 

and lung cancer. The Shanghai study includes occupational data and urine samples. 

Additional case-control studies of renal, pancreatic, bladder, and brain cancers, 

colon polyps, and second tumors are in progress in various national and international settings. The National Health and Nutrition Examination Survey (NHANES 

III) provides a population-based sample, with available serum and DNA that may 

prove useful in the future to conduct studies of the genetics of smoking and related 

traits. Results from these cohort studies will provide critical information that can be 

translated into effective prevention and treatment practices. 

Supporting Epidemiological and Genetic Research 

Lead investigators in the area of individual susceptibility to tobacco-related cancers 

have established a large database of epidemiologic, clinical, and laboratory data 

from over 3,000 study participants with and without lung cancer. Using advanced 

technologies, the researchers are assessing biomarkers to track the damaging effects 

of cigarette smoking. Investigators have recently reported an increased risk of lung 

cancer in people with genetic polymorphisms in the genes that eliminate carcinogens 

or repair DNA damage. Emerging technological advances will permit investigators 

to analyze the network of relationships among genetic, molecular, and environmental elements that control how tobacco damages individuals. For example, genetic differences that affect lung cancer risk may be used to identify highly susceptible subgroups and facilitate development of targeted intervention and prevention strategies. 

40 The Nation’s Investment in Cancer Research 
Lots of my friends In February 2003, NCI took the lead with other Federal and non-Federal partners to convene 

smoke — me, too. a meeting of experts to assess the state of knowledge about tobacco use and tobacco relatIt’s social, it’s relaxing, ed cancers among women. They identified priorities for research, evidence-based intervenand it keeps the weight tions, and the application of new and proven interventions across several key areas: 

off. And it’s not a • Toxicology, cancer susceptibility, and biologic gender differences related to tobacco and 

problem, I could quit cancer 

anytime. • The biology and behavior of addiction 

•	 National surveillance of tobacco use and control efforts 

•	 Prevention of tobacco use and treatment of addiction in women 

•	 Public knowledge of tobacco addiction, health and addiction risks, and control 

interventions targeting women 

•	 Community, policy, legal, and regulatory interventions 

•	 International issues in tobacco use and control 

Recommendations are being developed to serve as the basis for an action plan. 

This People’s Story is an amalgam of individual experiences. 

The health of former smokers, who now comprise about half of those diagnosed 

with lung cancer, is a special concern to NCI. Through targeted initiatives released 

over the past several years, NCI is funding studies to identify newer, more potent 

agents to prevent cancers in former smokers. Preclinical studies focus on identifying 

and prioritizing agents that prevent cancers in tobacco-susceptible organ systems, 

and clinical researchers are evaluating the efficacy of chemopreventive agents in 

specific cohorts of former smokers. 

Development Developing and Evaluating Innovative Interventions 

NCI supports translation of knowledge unveiled by research findings into interventions to benefit all people affected by or at risk for tobacco use and/or tobacco-related 

cancers. 

•	 NCI recently established the Tobacco Intervention Research Clinic to conduct 

innovative, state-of-the-science research on behavioral and pharmacological 

tobacco-use treatment interventions in clinical patient populations. The clinic’s 

streamlined funding and review process allows high-priority topics in tobaccouse treatment to be addressed in a timely fashion. 

•	 NCI and the National Institute on Drug Abuse (NIDA) have established the 

Working Group on Medication Development for Nicotine Addiction for 

exploring ways to advance progress in treatment for nicotine addiction. 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 41 
RESEARCH ON TOBACCO AND TOBACCO-RELATED CANCERS 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Understand the 

causes of tobacco 

use, addiction, and 

Discovery 

1. Lead and conduct a vigorous research and public health effort consistent with 

the enormous burden of tobacco-related disease. $33.50 M 

tobacco-related 

cancers, and apply 

■ Continue support for the Transdisciplinary Tobacco Use Research Centers (TTURCs) program, in 

collaboration with relevant public and private organizations. $10.00 M 

this knowledge 

to their prevention 

■ Support studies on the use of and cancer risk from tobacco products intended to reduce harm. 

$2.00 M 

and treatment. 

■ Support clinical and population studies that investigate the genetic, biological, and behavioral 

factors influencing vulnerability to tobacco dependence and tobacco-related cancers. $6.00 M 

■ Continue support for including questions on tobacco use in the Current Population Survey and 

expand efforts to translate the questions into languages such as Chinese, Vietnamese, Korean, and 

others. $2.50 M 

■ Capitalize on the breadth of expertise across NIH institutes by supporting collaborative projects 

such as the identification of new treatments to prevent weight gain following smoking cessation at 

NCI’s Tobacco Intervention Research Clinic. $1.00 M 

■ Support use of advanced technologies (e.g., genomics, proteomics, and bioinformatics) in populationbased studies to elucidate the genetics of smoking, in collaboration with other NIH institutes and 

centers. $ 5.00 M 

■ Support the Tobacco Etiology Research Network, a transdisciplinary network of scientists working 

to discover the causes of tobacco use and addiction among youth and young adults. $3.00 M 

■ Support studies that systematically examine tobacco constituents, genetic factors, and environmental and psychosocial risks and their relative effects on trajectories in tobacco use, cessation, 

relapse, and addiction in understudied and underserved populations. $3.00 M 

■ Collaborate with the American Cancer Society on tobacco use prevention and cessation research 

in China. $1.00 M 

Development 

2.	 Support and develop innovative, integrated studies and interventions to 

understand, prevent, and treat tobacco use and addiction. $23.00 M 

■ Accelerate the identification of new treatments for tobacco addiction through the implementation of 

a drug development and clinical trials collaborative group by NCI and other NIH institutes, as well 

as through linkage to existing clinical trial networks. $2.00 M 

■ Develop and implement a rapid-response surveillance system for emerging trends in tobacco use 

and tobacco-related disease through collaborative efforts. $1.00 M 

■ Expand the Cancer Intervention and Surveillance Modeling Network (CISNET) to develop models of 

tobacco use, dependence, relapse, and disease development. $2.00 M 

■ Support interdisciplinary studies to accelerate development of new, molecularly based lung cancer 

treatments and chemoprevention interventions. $10.00 M 

■ Accelerate the development of network-centric approaches, such as networks for monitoring 

tobacco use and reducing tobacco-related disparities, to assure maximal linkage and collaboration 

across tobacco control domains (e.g., surveillance, treatment). $4.00 M 

42 The Nation’s Investment in Cancer Research 
■ Continue to support research and analysis of tobacco industry documents through reissuance of a 

program announcement with review (PAR). 

■ Support prevention intervention research that addresses the common risk factors for youth problem 

behaviors, including tobacco use. $2.00 M 

■ Support tobacco use prevention and cessation research specifically addressing ethnically diverse 

underserved youth and young adults. $2.00 M 

Delivery 

3.	 Apply cutting-edge research to prevent and treat tobacco use and tobaccorelated cancers and to inform public health policy. $18.00 M 

■ Develop integrated and coordinated efforts to implement the youth and adult cessation Blueprint 

recommendations1 in collaboration with the Centers for Disease Control and Prevention and other 

public and private organizations. $2.00 M 

■ Award supplements to Cancer Centers to address disparities related to the clinical care of patients with 

tobacco-related cancers. $2.00 M 

■ Enhance the Cancer Information Service’s smoking cessation services and research infrastructure 

to improve treatment of tobacco addiction. $4.00 M 

■ Fund community-based, participatory research on tobacco-use prevention and cessation. $5.00 M 

■ As state tobacco control efforts decrease, support the development of multi-level secondary analyses, 

analytical tools, methodologies, and resources necessary to track and evaluate progress in state 

tobacco control and to benefit the delivery of tobacco control interventions in states. $2.00 M 

■ Support the identification, development, and dissemination of effective tobacco-use prevention and 

cessation interventions to underserved populations. $3.00 M 

Management and Support 	 $ 0.50 M 

Total $75.00 M 

1 National Blueprint for Disseminating Evidence-Based Clinical and Community Strategies to Promote Tobacco-Use Cessation, 2002. 

A Plan and Budget Proposal for Fiscal Year 2005 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

43 
Delivery 

Smokefree.gov, 

launched in Fall 2002, 

offers science-driven tools, 

information, and support 

to smokers who want to 

quit. Cosponsored by NCI 

and CDC, the Website 

provides state and national 

resources, free materials, 

access to online cessation 

support, and a toll-free 

number (1-877-44U-QUIT) 

for telephone-based 

cessation support. 

•	 The National Conference on Tobacco and Health Disparities, held in December 

2002, was the first scientific gathering to convene researchers and practitioners 

with the purpose of developing a research agenda to eliminate tobacco-related 

disparities. 

•	 Women, Tobacco, and Cancer: An Agenda for the 21st Century, held in 

February 2003, provided a similar venue for a focus on current research on 

tobacco and tobacco-related cancers in women. (See pages 40-41). 

•	 NCI-supported researchers have developed an online guide to evidence-based 

measures for use in youth tobacco research interventions. 

Delivering Evidence-Based Interventions 

NCI’s Smoking and Tobacco Control Monographs have provided timely information about emerging public health issues in smoking and tobacco control and accelerated its dissemination to the scientific and public policy communities. Those Who 

Continue to Smoke: Is Achieving Abstinence Harder and Do We Need to Change 

Intervention? was released in May 2003. The document is a result of a set of analyses funded jointly by NCI and the Tobacco Control Section of the California 

Department of Health Services. The National Blueprint for Disseminating and 

Implementing Evidenced-Based Clinical and Community Strategies to Promote 

Tobacco-Use Cessation, a document that resulted from the collaborative work of 

10 public and private organizations, provides state-of-the-art research strategies for 

cessation interventions. 

Smoking-related NCI publications available to the public include Clearing the Air, a 

manual designed to help smokers quit; Clear Horizons, a quitting guide for those 

older than 50; and the recently published Spanish-language guide on smoking cessation, Guia para Dejar de Fumar. In addition, through NCI’s Multimedia Technology 

Health Communications Grants to Small Business, NCI has supported the development of a number of interactive CD-ROMs and Web-based applications designed to 

capture the attention of targeted population groups. Examples include Rebels: The 

Battle for a Smoke-Free Future, a CD-ROM game for high school students who 

smoke. The game includes a teacher’s manual and student handouts. Two additional products are Dig Deeper, a CD-ROM for tobacco use prevention in 10- to 12-yearolds, and the Appalachian Community Kit for Tobacco Prevention, a second-hand 

smoke project. The community kit includes brochures, fact sheets, and videos 

designed for Appalachian women, who influence smoking cessation in their homes. 

44 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 45

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS

The term “energy balance” refers to the integrated effects of diet, physical activity, and genetics on

growth and body weight over an individual’s lifetime. Scientists are increasingly aware of the importance of understanding the effects of energy balance on the development and progression of cancer

and on cancer patients’ quality of life after treatment. 

At a time when almost two-thirds of the U.S. population is considered overweight or

obese, international teams of scientists have assembled compelling evidence that as

overweight and obesity increase, and physical activity decreases, the risk of developing many cancers rises. A comprehensive 2002 international review by the

International Agency for Research on Cancer (IARC) summarized, for the first time,

the compelling evidence that prevention of obesity reduces risk for many of the most

common cancers such as colon, postmenopausal breast, uterine, and renal cell cancers and that physical activity reduces risk for colon and breast cancers. The IARC

report further estimated that 20 to 30 percent of some of the most common cancers

in the United States, including breast, prostate, colon, kidney, and uterine cancers,

may be related to overweight and/or physical inactivity. Other international findings

indicate that physically active people have a 50 percent decreased risk of colon 

cancer. Evidence from a large cancer cohort study based on results from almost 

1 million subjects argues that overweight and obesity in our Nation account for 

14 percent of deaths from cancer in men and 20 percent in women.

PROGRESS IN PURSUIT OF OUR GOAL

NCI is committed to providing leadership to advance energy balance research

through targeted investments, as well as through collaborations with public and private partners. NCI-supported research has revealed a number of important findings,

including: mechanisms by which diet, weight, and physical activity affect carcinogenesis; new methods for quantifying key health behaviors and their consequences;

and innovative means for evaluating progress through national and regional health

monitoring. Even so, much remains to be learned about research methods, mechanisms of energy balance-related cancer morbidity and mortality, and the interplay of

multiple energy-balance risk factors on cancer development.

Improving Research Methods

NCI and its partners are improving diet and physical activity measures, including

both self-reported and objective measures. Recent research includes the following:

• The Observing Protein and Energy Nutrition (OPEN) study, the largest of its

kind, used biomarkers of dietary intake to assess the accuracy of dietary assessment methods commonly used in epidemiology, intervention, and surveillance

research. The investigators found that self-reported intake measures used in

many studies are not sufficiently accurate. Further research will examine whether

these findings are true for diverse populations, for other dietary-report or physical

activity instruments, and across varying nutrients and food groups, as well as how

the measurement inaccuracies may affect ongoing prospective cohort studies.

Optimizing Energy Balance to Reduce the Cancer Burden

1 Fulfilling the Potential of Cancer Prevention and Early Detection. National Academies Press, 2003.

A 2003 Institute of Medicine

(IOM) report on cancer 

prevention and control

assigns top priority to the

development of a national

strategy to prevent obesity

and sedentary behavior, 

second only to efforts to

curtail tobacco use.1

However, because proven,

evidence-based methods of

preventing these unhealthful

conditions are lacking, we

must begin by learning 

more about energy balance

through comprehensive 

and effective research. 

Discovery

Teams investigating energy

balance employ resources

ranging from preclinical

models to epidemiologic

studies and clinical 

interventions. 
Researchers are using breast 

density measurements as 

a marker for breast cancer 

risk to evaluate interventions 

that target pathways 

such as estrogen or insulin 

metabolism to reduce 

breast cancer risk. 

•	 The NIH Behavioral Change Consortium studies, cofunded by NCI, provided a 

setting for researchers to validate NCI-developed short screening questionnaires 

to assess changes in intake of fats, fruits, and vegetables. This and other research 

highlighted a need for innovation in measurement of diet and physical activity. 

In response, NCI is sponsoring the first NIH-wide program to improve diet and 

physical activity assessment methodology across culturally diverse populations. 

Discovering Mechanisms 

Researchers are discovering the mechanisms by which sedentary behavior or insufficient amounts of physical activity, poor diet, and overweight or obesity increase 

an individual’s risk for cancer from infancy through adult life. For example: 

•	 Investigators discovered that leptin, a hormone that tends to be elevated in obese 

people, provides researchers with a more precise means of studying the relationship between estimated total body fat and cancer. For example, using leptin 

measurements, researchers were able to establish a link between total body fat 

and the risk of developing prostate cancer. Prior studies using measurements 

such as weight or body mass had been unable to make this association. 

•	 Preclinical investigators using Mouse Models of Human Cancers Consortium 

(MMHCC) mice discovered that increased activity was more protective in 

male than female mice. 

•	 Intramural and extramural clinical researchers are exploring the ways that 

chemopreventive agents, diet, weight, and physical activity affect cancer 

development in humans. 

•	 Another team of investigators found that postmenopausal women participating in a 1-year physical activity intervention program experienced beneficial 

changes in total body fat, body fat distribution, and levels of circulating 

hormones. This discovery may lead to interventions to prevent hormonedependent cancers, such as breast and endometrial cancers. 

Evaluating Multiple Risk Factors 

Researchers evaluating multiple risk factors have found that the effect of women’s 

body mass index on colon cancer risk changes, depending on estrogen exposure. In 

addition, results from the Women’s Health Initiative, which examined the effects of 

obesity and physical activity on postmenopausal breast cancer risk, demonstrated 

that being physically active is most protective among women who remain of normal 

weight after menopause. This protection was not observed among obese women. 

Understanding the Role of Physical Activity and Diet 

In the last 5 years, scientists have improved their understanding of the relationship between physical activity and cancer, leading to critical insights into strategies to reduce the incidence and burden of cancer. For example: 

•	 Recent discoveries highlight the role genetic differences may play in individuals’ 

capacity to exercise as well as their risk for obesity. Now scientists must 

incorporate genetic information into large population studies to understand 

how the interplay of genetics with diet, obesity, and physical activity may 

alter cancer risk. 

46 The Nation’s Investment in Cancer Research 
•	 Among cancer patients and survivors, anecdotal and research evidence suggests that physical activity benefits cardiopulmonary function and quality of 

life, reduces fatigue and depression, and improves muscular fitness. Low- to 

moderate-intensity regular physical activity programs may help breast cancer 

patients maintain functional ability and minimize weight gain. This in turn 

may help prevent disease recurrence and other comorbidities. NCI and partners are exploring the potential benefits of weight control and physical activity 

interventions among diverse groups of cancer patients with breast, prostate, 

and colon cancers, as well as among long-term survivors of childhood cancer. 

Development Learning How to Change Behaviors 

As a first step in the development of energy balance interventions, NCI is 

researching key determinants of behavior change. This research has brought to 

light the difficulty of treating obesity once it has developed, and further reinforces 

the need for obesity prevention research, particularly among children and adolescents. Although much is known about how dietary and physical activity behaviors can be changed, attempts to develop behavioral interventions to effectively 

increase physical activity are relatively new. Therefore, NCI is sponsoring an 

NIH-wide effort to accelerate research on the mechanisms of physical activity 

behavior change. In addition, NCI has worked with groups such as the Agency 

for Healthcare Research and Quality and the National Academy of Sciences to 

conduct research reviews, providing information to aid evidence-based intervention development for dietary and physical activity behaviors. 

Developing Health Monitoring Systems 

NCI supports research to develop enhanced health monitoring systems at the 

national and regional levels to evaluate progress in cancer control across diverse 

populations, including minority and underserved populations. For example: 

•	 NCI included physical activity monitoring in the 2003 National Health and 

Nutrition Examination Survey (NHANES) to address discrepancies discovered 

in previous studies between reported and objective measurements of physical 

activity. Researchers will compare reported physical activity levels to measurements such as body composition and cardiovascular fitness, generating the 

first critically objective examination of physical activity data on a nationally 

representative sample. In addition, NCI-supported research has enhanced 

methods for evaluating usual food and nutrient intake in national populations. 

•	 NCI-sponsored research has demonstrated that the structure of neighborhood 

environment, such as availability of sidewalks, may enhance walking. NCI is 

partnering with the Centers for Disease Control and Prevention to collect data 

on diet, weight, physical activity, and neighborhood environment to determine 

whether there is a relationship among these factors in some communities. 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 47 
OPTIMIZING ENERGY BALANCE TO REDUCE THE CANCER BURDEN 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Understand the Discovery 

causes of adverse 1. Discover how body weight, physical activity, and diet, along with genetic and 

patterns of weight, environmental factors, interact over a lifetime to influence the cancer process. $18.00 M 

physical activity, and ■ Discover and characterize mechanisms leading to cancer by initiating transdisciplinary research cendiet; define their ters in the areas of energetics, physical activity, nutrition, and genetics. $6.00 M 

contributions to 

cancer; and apply 

this knowledge to 

■ Collect enhanced self-report and objective measures on diet and bioactive food components, body 

mass and composition, and physical activity and fitness by expanding and using existing population-level studies, including the Cohort Consortium. $5.00 M 

cancer prevention 

and control. 

■ Advance understanding of cancer mechanisms by conducting studies in existing NIH clinical metabolic and nutrition research units. $1.00 M 

■ Document the influence of energy balance on the cancer process throughout life through the use of 

preclinical animal models. $3.00 M 

■ Study the impact of energy balance on cancer by initiating basic and clinical research utilizing 

proteomic approaches and molecular technology. $3.00 M 

2. Monitor trends in and determinants of diet, weight, and physical activity and 

their cancer-related consequences across diverse populations by expanding 

nationwide research and health surveillance infrastructure. $12.50 M 

■ Expand nationwide surveys to enhance self-report, biologic, and genetic measures for monitoring 

and examining the impact of behaviors related to energy balance and cancer, in collaboration with 

the National Center for Health Statistics (NCHS). $2.00 M 

■ Advance knowledge about specific local populations by fostering community surveillance on individual behaviors and environmental factors, in collaboration with the Centers for Disease Control and 

Prevention and NCHS. $3.00 M 

■ Develop an infrastructure to train future national and international scientific leaders on the importance of energy balance across the cancer continuum by supporting interdisciplinary training in both 

basic and population sciences. $2.50 M 

■ Evaluate public comprehension of health recommendations on physical activity and nutrition through 

the NCI Health Information National Trends Survey (HINTS). $0.50 M 

■ Establish surveys of healthcare providers to evaluate knowledge, attitudes, and practice related to 

weight control in clinical practice. $1.00 M 

■ Identify opportunities for cancer control by developing a research resource on legislative policies 

related to nutrition, physical activity, and obesity. $1.00 M 

■ Initiate innovative research on economic factors related to diet, physical activity, and energy balance 

in at-risk populations, in collaboration with Federal partners, including the U.S. Department of 

Agriculture. $2.50 M 

48 The Nation’s Investment in Cancer Research 
Development 

3.	 Develop improved measurement of body mass and composition, physical 

activity and fitness, and diet and bioactive food components through selfreport measures and advances in technology for objective reference measures. $13.50 M 

■ Expand validation research of diet, physical activity, and fitness measurement through the use of reference biomarkers and physical measures of fitness within national and international cohort studies. 

$5.00 M 

■ Support research in collaboration with other NIH institutes in innovative technologies, such as electronic handheld monitoring devices and Internet surveys, in the assessment of diet, weight control, 

and physical activity behaviors. $2.00 M 

■ Improve the ability to capture information on diet, weight, and physical activity behaviors across 

diverse cultural populations. $5.00 M 

■ Develop surrogate (intermediate) biomarkers for use as predictors of the effectiveness of diet and 

physical activity interventions. $1.50 M 

4.	 Improve cancer-related health outcomes, especially in high-risk populations, 

by accelerating research on energy balance-related behaviors and developing 

interventions. $13.00 M 

■ Support research on interventions that focus on weight control through diet and physical activity in 

cancer patients and in populations at high risk for cancer. $4.00 M 

■ Support research to understand how sociocultural factors influence adoption of recommended 

behaviors, and develop approaches to improve interventions in specific populations. $3.00 M 

■ Develop effective approaches to improving and targeting health messages in the areas of dietary 

guidance, physical activity recommendations, and food labeling by supporting health communication research in partnership with other NIH institutes. $2.00 M 

■ Support research within transdisciplinary research centers on innovative and cost-effective obesity 

prevention interventions, with broad population impact at the social-environmental or policy level for 

children and adults. The research on efforts targeting adults should focus on critical periods when 

weight gain is likely to occur, such as with smoking cessation, pregnancy, stress, depression, injury, 

or cancer treatment. $4.00 M 

Management and Support $ 0.80 M 

Total $57.80 M 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 49 
I’ve struggled with my weight 

since I was about 13. 

I gain, I lose, I gain again. . . . 

I know the extra weight 

heart disease and diabetes, 

saying I’m also at higher risk 

for many cancers. 

for me to build new habits. 

The evidence is now clear that obesity is a significant risk factor in many cancers, 

cell. It has been estimated that overweight and obesity in the United States may 

Scientists have identified obesity and sedentary lifestyle as two important and modifiand specific cancers and cancer in general, and to devise ways to communicate this 

transdisciplinary 

populations. 

50 

makes me more likely to have 

but now the scientists are 

I try to eat right and exercise 

regularly, but it’s really hard 

including cancers of the colon, prostate, postmenopausal breast, uterine, and renal 

account for 14 percent of all cancer deaths in men and 20 percent in women, adding 

up to more than 94,000 deaths each year. 

Researchers suspect that many of the mechanisms responsible for this increased risk 

are systemic in nature, simultaneously increasing the risk of cancer in many parts of the 

body. For example, overweight and inactivity have been shown to cause the body to 

secrete increasingly higher amounts of insulin and other growth factors. Cells exposed 

to high levels of these substances over an extended period are more prone to accelerated growth. This rapid growth increases the likelihood of random genetic mutations 

which, in turn, elevates the risk of cancer. 

Other mechanisms related to energy balance appear to be specific to certain cancer 

types. For example, investigators have demonstrated that exercise decreases colon 

cancer risk, possibly by increasing the rate at which harmful waste products move 

through and exit the colon. Also, epidemiologic researchers have shown that overweight or obese women, especially those who gain weight throughout adulthood, 

experience increased risk for breast cancer after menopause. Even moderate regular 

exercise may help reduce this risk by decreasing estrogen levels in the breast tissue. 

able risk factors for cancer. Experts believe that it is particularly important to reach 

children with information about healthy eating and regular exercise while their lifestyle 

patterns are developing and before they experience excess weight gain. 

NCI is working to accelerate our understanding of the many aspects of energy balance 

information to all populations. Investigators are examining the relationship between 

cancer and the independent and combined effects of reduced energy intake (caloric 

restriction), various components of diet (e.g., carbohydrates, protein, fat), specific 

foods, micronutrients, food preparation methods, and types and intensity of physical 

activity. To further this research, NCI is hoping to support more

research dedicated to improving our understanding of how energy balance affects 

risk across the cancer continuum, from causation through survival, and on developing 

innovative approaches to obesity prevention, especially among children and in diverse 

This People’s Story is an amalgam of individual experiences. 

Energy In, Energy Out – A Critical Balance 

The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 51

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS

Improving the Quality of Cancer Care

Receiving the best possible medical treatment and care is the continuing hope for over 9 million cancer

patients and survivors in the United States. Drawing from the Institute of Medicine’s (IOM) National

Cancer Policy Board (NCPB) report, we define quality cancer care as the provision of evidence-based,

patient-centered services throughout the continuum of care in a timely and technically competent

manner, with good communication, shared decision making, and cultural sensitivity. The ultimate aim

is to improve a range of outcomes important to patients, families, and other decision makers, including patient survival and health-related quality of life. 

Unfortunately, far too many will not receive the highest caliber of care. In many

cases, there is substantial disagreement about what constitutes optimal care, especially from the patient’s perspective, and about the best approaches for achieving

improvement. Even where consensus appears to exist, there is often wide variation

in practice patterns. Therefore, it is critical that we advance understanding of how

to measure, monitor, and improve the quality of cancer care. 

The reasons why some cancer patients do not receive the newer, more effective

treatments or sufficient palliative and end-of-life care are not adequately understood. The NCPB has criticized the Nation’s “ad hoc and fragmented cancer care

system.” Cancer patients, families, and providers gave testimony, summarized in

the President’s Cancer Panel Report, Voices of a Broken System: Real People, Real

Problems,1 which identified barriers to high quality cancer care. They include system and financial limitations, inadequate patient information and provider education, poor management of cancer-related symptoms, and lack of timely referral to

palliative and hospice care.

NCI must strive to discover what constitutes quality cancer care. We must develop

the measures and tools required to achieve improvements and evaluate performance. Finally, we must investigate and generate mechanisms, in collaboration with

public and private policymakers, to ensure that quality care — based on outcomes

research that identifies best practices — is delivered to all who need it. 

PROGRESS IN PURSUIT OF OUR GOAL

Discovering What Constitutes Quality Cancer Care

Several NCI-supported national data resources enable researchers to empirically

explore important questions related to cancer quality of care. Rapid Response Special

Studies (RRSS) allow NCI to quickly sponsor research on high priority topics. A

recent RRSS study found that in children with cancer, 71 percent of patients

younger than 15 received treatment through NCI-sponsored clinical trial protocols,

but less than 24 percent of adolescents ages 15-19 received this highest quality

pediatric cancer treatment. 

Discovery

1 Institute of Medicine, National Research Council, Improving Palliative Care for Cancer, 2001.

President’s Cancer Panel, Report of the Chairman 2000-2001, Voices of a Broken System: Real People, Real Problems,

September 2001.
Two new RRSS studies, the Experience of Care and Health Outcomes of Survivors 

of Non-Hodgkin’s Lymphoma (ECHOS-NHL) and the Assessment of Patients’ 

Experience of Cancer Care (APECC), will yield important new information about 

the follow-up care experiences and health outcomes of cancer survivors. 

NCI’s Patterns of Care/Quality of Care (POC/QOC) program draws from the 

Surveillance, Epidemiology, and End Results (SEER) registry data to investigate 

adoption of recommended treatments for the most common cancers. The results of 

POC/QOC studies are reported at professional meetings of oncology societies and 

are used to develop educational and training opportunities to improve the use of 

state-of-the-art cancer therapy in community practice. Currently, POC/QOC data 

are being analyzed to document the relationship between health insurance coverage 

and receipt of appropriate or complete cancer care. 

Studies linking SEER and Medicare data continue to provide insights into quality 

of care issues: 

•	 Hospice is used more frequently and for a longer period by persons enrolled in 

health maintenance organizations (HMOs), compared with fee-for-service 

patients. 

•	 Patients diagnosed with superficial bladder cancer undergo significantly less 

postdiagnostic surveillance than generally recommended by leading cancer 

professional and research organizations. 

•	 Disabled women with breast cancer are diagnosed at a later stage of the disease 

than nondisabled women, with the disparity greater for women with fee-forservice coverage compared with HMO coverage. 

To better understand the causal factors and mechanisms that underlie the patterns 

of care described in these investigations, NCI has established large national-level 

studies that track patterns of care and outcomes for cohorts of newly-diagnosed 

cancer patients. The first of these, the Prostate Cancer Outcomes Study (PCOS), 

provided a wealth of information about treatment outcomes for 3,500 men diagnosed 

with tumors confined to the prostate gland. 

In 2001, NCI launched the Cancer Care Outcomes Research and Surveillance 

Consortium (CanCORS), combining data from registries, medical records, insurance claims, and patient and provider surveys to create an unusually rich longitudinal picture of the care received by a sample of 5,300 colorectal and 4,800 lung 

cancer patients across the United States. Treatment settings include fee-for-service, 

large nonprofit HMOs, and the relatively centralized health care system of the 

Department of Veterans Affairs. 

The Breast Cancer Surveillance Consortium (BCSC) investigates factors associated 

with high quality screening mammography in community practice. Evidence from 

a study involving over 300,000 women, including 2,200 women with cancer, examined the combined and individual effects of breast density, age, and hormone 

replacement therapy on the accuracy of screening mammography. Research examining 

52 The Nation’s Investment in Cancer Research 
Development 

NCI initiatives are 

significantly expanding our 

understanding of how to 

measure and improve the 

quality of cancer care 

in a variety of specific, 

community-based practice 

settings. But we need additional research on health 

system-level interventions. 

The organizational and 

informatics infrastructure of 

clinical and patient decision 

making requires improvement, and patient care will 

benefit from incentives 

rewarding the delivery of 

evidence-based cancer care. 

the biologic characteristics of cancers that are not detected by screening has found 

that screening mammography may miss some rapidly growing, high-grade tumors 

and those of lobular or mucinous histology. BCSC is actively collaborating with 

Federal regulatory agencies, radiological professional societies, and private-sector 

vendors to reduce the cost and improve the quality of data collection for mammography quality control. 

The Cancer Research Network, a consortium of researchers affiliated with 11 major 

not-for-profit HMOs, is providing the mechanism for NCI to quickly obtain better 

data on patterns of cancer care from multiple perspectives. Recent findings include: 

•	 Support for tobacco cessation is both variable and suboptimal. 

•	 The most important factor predicting oncologists’ ability to recruit patients to 

clinical trials was having sufficient organizational infrastructure to support trial 

participation. 

•	 The majority of both breast and cervical cancer cases appear to be associated 

with an absence of screening and failures in detection. 

The NCI National Clinical Trials Program provides an ideal venue to deepen our 

understanding about the quality of cancer care from both biomedical and patientreported perspectives by incorporating clinical and health-related quality of life 

endpoints into clinical study design. 

Developing Core Measures to Support Discovery and 

Delivery of Quality Cancer Care 

In 2001, NCI convened the Cancer Outcomes Measurement Working Group 

(COMWG), composed of 35 internationally recognized experts in measurement, 

oncology, and the social sciences. This group assessed alternative approaches for 

improving patient-centered outcome measures such as health-related quality of life, 

economic burden, and satisfaction with care. The lack of standardization in measuring such patient-reported outcomes is a major barrier to comparing findings in 

quality of care research. In the forthcoming volume Outcomes Assessment in 

Cancer (Cambridge University Press, 2004), the working group emphasizes the 

potential value of survey item banks and computer-adaptive data collection. 

NCI is collaborating with other Federal agencies and the private sector to create 

standards for process measures of cancer care quality. The centerpiece of this 

Cancer Care Quality Measures Project (CanQual), conducted under the auspices of 

the nonprofit National Quality Forum (NQF), is consensus development of core 

process measures and recommendation of topics for further measures development. 

The high-priority areas identified by NQF are: diagnosis and treatment for breast, 

colorectal, and prostate cancers; access to care; communication and coordination of 

care; and symptom management across the cancer continuum, including end of life. 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 53 
Delivery 

A workshop on the diffusion 

of medical innovations will be 

held in 2004, setting the stage 

for studies to examine why 

some highly promising therapies successfully move into 

clinical practice while others 

do not. 

Developing Approaches to Improve Symptom Management and 

Palliative Care across the Cancer Continuum 

The Improving Palliative Care for Cancer report2 identified gaps in symptom 

management and palliative care research. Information on how to better measure, 

evaluate, and improve symptom management is now emerging. Basic and clinical 

researchers are currently: 

•	 Determining which symptoms occur most frequently according to tumor type 

and treatment choice. 

•	 Developing new methods for assessing symptoms. 

•	 Working to improve communication about symptoms between patients and 

their health care teams. 

•	 Developing and comparing strategies of symptom management. 

•	 Finding ways to better integrate symptom management as a vital part of all 

cancer care. 

Delivering on the Promise of High Quality Cancer Care through 

Evidence-Based Decision Making 

Since it was established in 2000, NCI’s Quality of Cancer Care Committee (QCCC) 

has sought to improve Federal-level decision making on cancer care. Through the 

QCCC, NCI is currently supporting three interagency projects: 

•	 The Health Resources and Services Administration, the Centers for Disease 

Control and Prevention, and the nonprofit Institute for Health Care 

Improvement are collaborating with NCI to improve screening and follow-up 

for breast, cervical, and colorectal cancers in community health centers for the 

medically underserved. In the project’s pilot phase, 12 health centers helped 

develop and test a core set of quality performance measures, which are now 

being evaluated in 20 additional centers. 

•	 The Centers for Medicare and Medicaid Services is working with NCI to 

increase the awareness and improve the delivery of Medicare-covered colorectal cancer screening services. 

•	 The Department of Veterans Affairs (VA), with NCI support, has established 

a Quality Enhancement Research Initiative (QUERI) to improve screening, 

follow-up, treatment, and end-of-life care for colorectal cancer in the VA 

health system. 

2 Institute of Medicine, National Research Council, Improving Palliative Care for Cancer, 2001. 

54 The Nation’s Investment in Cancer Research 
Symptom Management Research – 

Improving Quality of Life for Patients and 

Their Caregivers 

Each time my colon cancer 

comes back, it seems to hit 

me harder. The pain is worse, 

I have more trouble sleeping, 

and I just get so tired. The 

pain is the biggest problem. 

I get depressed because 

I can’t control it. When the 

doctors and nurses ask me 

how the pain is, I don’t know 

how to describe it, except 

that it’s worse than it was the 

week before. I’m afraid to say 

too much, because they might 

stop the chemo, and then the 

cancer would get even worse. 

Symptoms of cancer and side effects of related treatments can be severe in patients 

with advanced-stage disease, especially in those receiving aggressive and experimental therapies. Research has shown that symptoms affect patients’ overall quality of life, 

including their ability to do many of the things most people take for granted, such as 

caring for themselves, doing household chores, sleeping, or going to work. We know 

that intense and uncontrolled symptoms lead to poor emotional and physical health. 

We also know that patients are sometimes hesitant to report they have bothersome 

symptoms for fear their therapy will be slowed or stopped. More symptom management research is needed to ensure that patients receive quality, effective cancer care 

that does not disrupt their quality of life. (See pages 54 and 57.) 

NCI-supported researchers are exploring ways to help patients and their families better manage symptoms 

and improve their quality of life. Investigators are seeking a better understanding of the interaction between 

common symptoms of advanced cancer. For example, when patients experience pain, are they more likely to 

have fatigue? And which symptoms are particularly troubling to caregivers and patients? 

My husband has been battling 

cancer for a year and a half. 

I know he’s in a great deal of 

pain because I can see it in his 

face. The doctor gave him 

pain medication, but I wonder 

if he’s taking the full dose — 

he’s told me before he doesn’t 

like how “out of it” he feels 

when he takes it. It seems like 

it’s a never ending cycle — 

as the pain gets worse, he 

gets more tired, he can’t eat 

or sleep, which makes the 

pain even harder to take. 

I wish I knew what to do to 

help him be more comfortable. 

Over 12 million Americans are providing care for a family member with cancer. These 

caregivers are partners in care, part of the patient’s team, and a vital resource to the 

patient. They are often responsible for accessing information, communicating with the 

patient’s health care team, and providing hands-on care to alleviate troublesome 

symptoms. Caregivers are more likely to feel a greater sense of burden and to be 

depressed, frustrated, and overwhelmed in their role when patients’ symptoms are out 

of control, particularly when the patient has severe pain or fatigue. Through symptom 

management research, we will be able to better prepare caregivers to manage patients 

at home and ultimately improve caregivers’ emotional and physical health as they 

continue to help their family members live with cancer. 

This People’s Story is an amalgam of individual experiences. 

A Plan and Budget Proposal for Fiscal Year 2005 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

55 
IMPROVING THE QUALITY OF CANCER CARE 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Improve the quality Discovery 

of cancer care by 1. Strengthen the methodological and empirical foundations of cancer care 

strengthening the quality assessment. $17.50 M 

scientific basis for ■ Investigate factors associated with high-quality screening mammography in community practice, by 

public and private renewing support for the Breast Cancer Surveillance Consortium (BCSC). $6.00 M 

decision making in 

care delivery, 

■ Support intervention studies and programs for improving referral patterns and treatment where suboptimal performance has been documented, such as in cervical and ovarian cancer. $2.00 M 

coverage, purchasing, 

regulation, and 

standards setting. 

■ Investigate the feasibility of implementing new data systems to monitor the outcomes and economic 

cost of cancer care in healthcare systems, including: 

— Linkage of tumor registry information with additional public and private health claims data and 

with patient outcomes and satisfaction surveys. $5.00 M 

— Establishment of physician networks and databases for tracking and monitoring cancer 

screening practices. $1.50 M 

— Creation of a provider survey initiative to collect nationally representative data from practitioners 

and health care organizations. $1.00 M 

■ Conduct new studies to strengthen the methodological foundations of outcomes research and 

quality of care assessment. $2.00 M 

2. Enhance quality-of-care research within, and beyond, the NCI clinical trials 

program. $2.00 M 

■ Conduct an international state-of-the-science conference on the benefits of adding quality of life and 

outcome measures to cancer trials, in collaboration with the Food and Drug Administration and 

community-based practitioners. Recommend new guidelines for NCI-supported treatment and 

prevention trials. $0.50 M 

■ Examine the adoption of therapies across delivery systems, using knowledge gleaned from a 

workshop on the diffusion of medical innovations. $1.00 M 

■ Support economic studies paralleling cancer treatment and prevention trials and other cancer 

control intervention studies. $0.50 M 

■ Strengthen the evaluation of proposals to use health-related quality of life and economic endpoints 

in NCI-sponsored Phase III trials, by establishing protocol review teams consisting of both NCI and 

non-NCI experts. 

Development 

3.	 Identify, develop, and test core process and outcome measures for assessing 

the quality of cancer care. $6.50 M 

■ Improve patient-centered outcomes measurement, including health-related quality of life and patient 

satisfaction, by (1) developing and testing tools and instruments; (2) supporting statistical studies to 

facilitate the “cross-walking” of scores among competing instruments, and determining clinically 

meaningful change scores; and (3) conducting pilot investigations of new or enhanced outcome 

measures. $2.00 M 

■ Identify and test additional core process measures by providing supplemental funding for the Cancer 

Care Quality Measures Project (CanQual). $2.00 M 

56 The Nation’s Investment in Cancer Research 
■ Test the ability of core process and outcome measures to improve the quality and patient safety of 

cancer care, strengthen provider accountability, and enhance informed decision making. $2.50 M 

4. Incorporate symptom management and palliative care into the full spectrum of 

cancer quality improvement research and translation efforts, from initial treatment, through survivorship, and at the end of life. $3.00 M 

■ Assess approaches for effective symptom management and palliative care by collaborating with 

other NIH institutes to support research on new interventions (e.g., for lymphedema, cachexia, pain, 

and sleep disorders). $2.50 M 

■ Assist in the coordination of Department of Health and Human Services end-of-life research through 

the creation of a symptom management and palliative care consortium within NCI Cooperative 

Groups, and cosponsor an NIH End of Life interest group. 

■ Increase the number of interdisciplinary-trained researchers in symptom management, rehabilitation, 

and palliative care through individual mentor and career development awards. $ 0.50 M 

Delivery 

5.	 Ensure that the best scientific evidence about quality measures and assessment informs Federal, state, and private-sector decision making about cancer 

care. Sponsor collaborative projects on core measures of cancer care quality 

and translate research evidence into better quality care. $6.50 M 

■ Provide technical assistance and advice to public agencies and private organizations, through 

continued support for the Quality of Cancer Care Committee (QCCC) and the clinical and policy 

expertise of the QCCC. $2.00 M 

■ Implement core process measures of cancer quality and monitor progress through collaboration with 

public agencies and private organizations. Such measures would include symptom management 

and palliative care. $1.00 M 

■ Incorporate and disseminate evidence-based symptom management and palliative care practices 

more fully into NCI’s education and information products for health professionals. $0.50 M 

■ Support ongoing development of a national cancer data system for tracking trends in cancer care 

and outcomes and identifying population disparities, through collaboration among QCCC members, 

the states, and private organizations. 

■ Strengthen the science of cancer care by: 

— Implementing and evaluating evidence-based interventions to improve cancer care through 

collaborative teams within NCI-designated Cancer Centers and other organizations. $1.50 M 

—	 Addressing the delivery of cancer care at the health systems level, including approaches to 

improve cancer care coordination, patient navigation, and provider decision support, by issuing 

joint solicitations with other NIH institutes and Federal agencies. $1.50 M 

Management and Support $ 0.80 M 

Total $36.30 M 

A Plan and Budget Proposal for Fiscal Year 2005 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

57 
58 The Nation’s Investment in Cancer Research

Overcoming cancer health disparities is one of NCI’s top priorities for reaching our Challenge Goal of

eliminating suffering and death due to cancer. It is well known and documented that the burden of

cancer is not borne equally by all population groups in the United States. One’s gender, ethnicity, and

socioeconomic status influence cancer incidence, morbidity, and mortality. For example:

• Men have about a 50 percent higher annual death rate from cancer than women. 

• African Americans and Alaskan Natives experience a higher incidence of colorectal,

lung, and bronchus cancers than any other ethnic group.

• The death rate from prostate cancer among African American men is approximately twice that of White men.

• Asian and Pacific Islanders, including Native Hawaiians, have a substantially

higher incidence of stomach cancer than other populations.

• People living in areas of low socioeconomic status generally have higher cancer

death rates than those in areas of higher socioeconomic status.

The scientific community has a critical and unique role in addressing the moral

and ethical dilemmas posed by the unequal burden of cancer in our society. We

must use our overall knowledge and understanding of cancer and our knowledge

of the fundamental causes of health disparities to develop and deliver effective

interventions to all Americans, particularly those who bear the brunt of the burden. This is an especially opportune time for NCI to commit additional resources

to address cancer health disparities. Innovations include the availability of new

technologies such as telemedicine, bringing screening and diagnostic services to

people where they live, the exciting potential for scientific advances in cancer prevention and treatment, and new developments in addressing the cancer communications needs of specific communities.

PROGRESS IN PURSUIT OF OUR GOAL

Bridging the Gap between Discovery and Delivery to Address Disparities

NCI-supported Special Population Networks (SPNs) at 18 institutions across the

country are building long-term relationships between large research institutions

and community-based programs to learn more about the causes of cancer disparities in minority communities and to develop and test ways to address and eliminate these causes. The SPNs are located in institutions that serve American Indian

populations in the Southwest, rural underserved populations of Appalachia,

Asian and Pacific Islanders in the West, and underserved and immigrant minority

groups in inner cities. The programs promote cancer awareness through culturally tailored education programs, encourage cancer screening and participation in

clinical trials, and conduct community-based cancer research.

To bring new radiation-related treatments for cancer to underserved communities,

NCI is providing support and resources for radiation oncology clinical research

in institutions that traditionally have not been involved in NCI-sponsored

research, but that care for a disproportionate number of medically underserved,

low-income, and ethnic and minority populations. Supported through the

Reducing Cancer-Related Health Disparities

From Discovery 

to Delivery

Over the past several 

years, NCI has increased 

its support for research to

address the gaps in the 

delivery of research

advances to all populations

regardless of their age, 

gender, race, ethnicity, or

socioeconomic status. 
The use of telemedicine 

in communities such 

as Native American 

reservations can 

significantly improve 

access to care. 

NCI assembled a think 

tank to synthesize research 

knowledge and identify 

core findings to provide 

Federal, state, and local 

policymakers with evidencebased recommendations 

to reduce disparity in 

cervical cancer mortality 

rates. 

Cooperative Planning Grant for Cancer Disparities Research, this initiative also 

has established partnerships between institutions that are actively involved in 

NCI-sponsored research. This support also provides for the use of telemedicine 

and teleconferencing systems between institutions and partners, including patient 

exam cameras and remote-controlled microscope capability to examine biopsy 

specimens, allowing for simultaneous examination and discussion. 

The Patient Navigator program, a new approach to providing individualized 

assistance to newly diagnosed cancer patients, is being piloted at two institutions 

supported through the Cooperative Planning Grant for Cancer Disparities 

Research. Patient navigators are trained, culturally sensitive individuals who help 

cancer patients manage the complexities of medical care by providing information and guidance on screening, diagnosis, and treatment options. Results of this 

pilot will provide NCI with a model for examining the effectiveness of promising 

interventions to address gaps in the delivery of cancer health services. 

NCI, in collaboration with four institutes and offices within the National Institutes 

of Health, recently provided support to establish Centers for Population Health and 

Health Disparities. Interdisciplinary in focus, these centers provide environments 

conducive to collaborations among biomedical, social science, and environmental 

research investigators working with communities serving low-income and racially 

diverse populations. The centers will accelerate knowledge about social, cultural, 

biological, behavioral, and environmental factors that contribute to health disparities, and the development of effective interventions to reduce them. 

Initiated in 1990, the Minority-Based Community Clinical Oncology Program 

(CCOP) continues to provide minority cancer patients with access to state-of-theart cancer treatment, prevention, and control technology in their own communities. The current program includes 11 minority-based CCOPs and involves more 

than 40 hospitals and over 100 minority investigators. Greater involvement in 

clinical trials research by African American, Hispanic, Asian American, American 

Indian, and other racial and ethnic minority patients is needed to ensure that 

advances in clinical research are extended to all groups and subsequent results can 

be generalized to the entire population. NCI issued an announcement in Spring 

2003 to continue support for this program. 

Broadening Our Understanding of the Causes of Cancer Disparities 

Despite a three-fold reduction in cervical cancer mortality nationwide in the past 50 

years, counties stretching from Maine southwest through Appalachia to the 

Texas/Mexico border, in many Southeastern states, and in the Central Valley of 

California have experienced persistently higher cervical cancer mortality rates. To 

address these high mortality rates, NCI has implemented a partnership demonstration 

project in eight states to increase cervical and breast cancer screening among women 

who have never or rarely been screened, in collaboration with the Centers for Disease 

Control and Prevention (CDC), the United States Department of Agriculture (USDA), 

and the American Cancer Society (ACS). Using NCI analyses of county mortality rates 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 59 
to identify high-rate counties, the partners are working together to train staff of 

CDC’s Breast and Cervical Cancer Early Detection Program; USDA’s Cooperative 

State Research, Education, and Extension Service; ACS’s regional cancer control 

programs; and NCI’s Cancer Information Service to use evidence-based cancer 

screening promotion programs to increase screening among high-risk women. 

Published studies in leading medical journals show that Black patients tend not to 

receive the same level of treatment quality as White patients of similar socioeconomic status, insurance coverage, health status, and diagnosis. Other studies show 

that other race and ethnic minorities experience similar treatment disparities. The 

unsettling nature of these conclusions led NCI to more thoroughly explore the 

mounting evidence of racial bias, prejudice, and intolerance in the Nation’s health 

care system. NCI conducted think tank meetings composed of experts from a variety of disciplines who could help shed light on a complex set of issues. The purpose 

of the first think tank was to plan an approach to understanding why patients of 

similar financial resources, health status, access, and other factors but of differing 

racial and ethnic backgrounds do not receive the same level of health care. A 

subsequent think tank addressed participants’ concerns regarding the depth and 

complexity of the problem in science and society. This think tank examined how 

evolution, migration, genetics, and social history have contributed to the problems 

associated with race in science. 

NCI supports numerous studies to identify risk factors for disease and describe 

racial and ethnic differences in cancer rates. For example: 

•	 The Southern Community Cohort Study (SCCS) is a landmark study that will 

further determine why African Americans are more likely to develop and die 

from cancer. A collaborative effort with public and private research-related 

organizations, the SCCS will examine disparities in lung, breast, colorectal, 

and prostate cancers by recruiting 70,000 African American and 35,000 

non-African American residents in the southern United States. 

•	 The association of diet and other factors contributing to gastric cancer is 

being studied in a 5-year, population-based case-control trial. Ethnic groups 

receiving special emphasis include Caucasians, Chinese, Filipinos, Hawaiians/ 

part Hawaiians, and Japanese. 

•	 A study of the causes of illness in Black women will examine multiple risk factors 

for cancer, cardiovascular disease, and other major illnesses. Possible risk factors to be examined include obesity, cigarette smoking, physical activity, alcohol 

use, diet, estrogen use, and reproductive factors. 

•	 Through the NCI-supported Center for Psycho-Oncology, investigators are 

looking at the interrelationships among biological processes, cognition, emotion, and physical health in ethnically and culturally diverse survivors of 

breast cancer, prostate cancer, and AIDS-related cervical cancer. 

60 The Nation’s Investment in Cancer Research 
In Spring 2003, NCI and DHHS announced a national campaign to reduce the risk 

of chronic diseases among African American men, encouraging the consumption 

of nine servings of fruits and vegetables a day. African American men are among 

the most seriously affected by diet-related chronic diseases such as cancer and 

have the lowest overall consumption of fruits and vegetables. The campaign 

includes national radio advertisements, brochures, and a new Website for African 

American men (9aday.cancer.gov).

Encouraging Minority Investigator Involvement in Cancer and 

Cancer-Related Disparities Research 

NCI continues to support opportunities to improve recruitment and retention of 

minority researchers in cancer and cancer-related health disparities research 

through a variety of programs. The Network for Cancer Control Research among 

American Indian/Alaska Native Populations focuses on increasing the number of 

Native American researchers, scientists, and medical students involved in cancer 

control activities. The Minority Institution Cancer Center Partnership reaches out 

to over 300 minority institutions to offer new opportunities for training minority scientists and to promote more research and community outreach on minority 

health at Cancer Centers. Interest in health disparities research within the Cancer 

Prevention Fellowship Program continues to grow. 

The purpose 

• 

• 

and intervention development. 

• 

clinical interventions, and evaluate their impact on specific cancer health disparities. 

• 

for every American. 

initiative. 

Health Disparities 

BROAD RESEARCH PRIORITIES: PUBLIC HEA LTH EMPHASIS 

NCI’s Progress Review Group process is serving as a model for a Trans-Department of 

Health and Human Services (HHS) effort to address health disparities. 

of the Trans-HHS Cancer Health Disparities Progress Review Group (CHD PRG) is to 

identify new opportunities for HHS agencies to address cancer health disparities, 

implement new initiatives toward that end, and evaluate their progress. This effort will serve as a demonstration 

project for possible replication in addressing health disparities in other diseases as well. 

The process is designed to: 

Comprehensively define and describe issues related to cancer health disparities. 

Identify areas of strength, gaps, opportunities, and priorities to address cancer health disparities in research 

Facilitate the adoption and implementation of evidence-based research, policy, community programs, and 

Ensure unbiased access to standard and continuous preventive care, early detection, and treatment of cancer 

A report and recommendations from the CHD PRG will be issued in early 2004 and will form the basis for HHS’s future 

planning to reduce cancer health disparities. Go to www.chdprg.omhrc.gov for more information on this trans-HHS 

Trans-HHS Initiative Applies 

Progress Review Approach to 

A Plan and Budget Proposal for Fiscal Year 2005 61 
REDUCING CANCER-RELATED HEALTH DISPARITIES 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Discover the 1. Implement recommendations from the Trans-DHHS Cancer Health Disparities 

fundamental causes Progress Review Group. (See page 61.) $5.00 M 

of health disparities Discovery

in cancer, develop 2. Expand research on the magnitude and causes of health disparities in cancer. $19.00 M 

effective interventions 

■ Support international collaborative studies on social determinants of cancer and cancer-related to reduce these disparities through supplements to NCI-supported Centers for Population Health and Health disparities, and Disparities. $2.00 M 

facilitate their delivery. 

■ Expand epidemiologic studies exploring racial/ethnic cancer disparities. $2.00 M Collaborate through


the discovery- ■ Conduct methodological research to ensure cross-cultural equivalence in survey, epidemiological,


development-delivery and clinical research involving cancer risk factors. $1.00 M


continuum to ensure 

continuous access to 

■ Collect risk factor and screening data for small populations defined by geographic, racial/ethnic, 

socioeconomic, and other characteristics. $4.00 M 

evidence-based and 

high quality cancer 

■ Examine the genetics of race, and develop policies that define the role of race in science through a 

trans-NIH study in partnership with the National Human Genome Research Institute. $5.00 M 

prevention, early 

detection, and 

treatment services 

■ Examine the national costs associated with cancer health disparities, and the cost of not treating all 

patients equally, by conducting a multidisciplinary study on the economics of cancer with the NIH 

Office of Behavioral and Social Sciences Research. $5.00 M 

for all Americans. 

Development 

3. Develop effective interventions to reduce cancer health disparities. $41.00 M 

■ Establish new and strengthen current collaborative research partnerships among the Special 

Populations Networks (SPNs), NCI Divisions, and other Federally funded research networks. $2.00 M 

■ Test community-based interventions leading to the reduction of disparities in cervical cancer mortality through collaborations with NCI’s SPNs in Appalachia, the South, and the Texas border. $5.00 M 

■ Reduce cancer health disparities through community partnerships, outreach, and training by continuing support for SPNs. Recompetition of the SPNs will emphasize bridging the gap between the 

discovery and development continuum of research and the delivery system of medical care in minority and underserved communities. $20.00 M 

■ Support research on planning, development, implementation, and evaluation interventions that provide access to timely and accurate cancer information, screening, early detection, and treatment in 

a variety of health care service delivery sites (e.g., examine the Patient Navigation Model as an effective intervention in populations experiencing serious cancer-related health disparities). $4.00 M 

■ Establish a Dissemination/Diffusion Research Grants Program to: 

— Study social, environmental, and behavioral barriers to the adoption of evidence-based cancer 

prevention and control interventions by public health officials and community clinicians. 

— Test new hypotheses for reaching underserved populations in under-resourced community health 

settings. 

— Develop, apply, and evaluate dissemination and diffusion interventions to reduce cancer health 

disparities. $4.00 M 

62 The Nation’s Investment in Cancer Research 
■ Increase the number of scientists with a focus on health disparities research by recruiting four additional minority scientists and/or physicians through the Cancer Prevention Fellowship Program. 

$1.00 M 

■ Encourage high school to graduate-level minority students to enter careers in health disparities 

research by expanding the Continuing Umbrella of Research Experiences Program and the Science 

Enrichment Program. $3.00 M 

■ Support efforts to improve recruitment and retention of minorities in NCI-supported 

clinical trial programs. $1.00.M 

■ Increase minority participation in clinical trials through an NCI fellowship training program for healthcare providers and through other forums. $1.00 M 

Delivery 

4.	 Facilitate implementation of new policy, community, and clinical interventions, 

and evaluate their impact on health disparities. $5.50 M 

■ Customize cancer information materials for targeted audiences by expanding NCI’s integrated 

low-literacy program. $1.50 M 

■ To address health disparities among medically underserved populations, support local and regional 

science/practice partnership demonstration projects, and disseminate models of success to 

communities with similar infrastructure barriers. $2.50 M 

■ To help move science into practice, expand Cancer Information Service Partnership Program 

resources to build new collaborations with staff from the American Cancer Society’s Division of 

Cancer Control and the Centers for Disease Control and Prevention-funded State Health 

Department Comprehensive Cancer Control Program. $1.50 M 

Management and Support $ 0.80 M 

Total $71.30 M 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 63 
NCI and NIA Launch New Efforts to 

Explore the Interface of Aging and Cancer 

The risk of developing cancer significantly increases with age and — as the 

population of older Americans expands in the next decade — the cancer 

burden will escalate. Close to 60 percent of all new cancers and 70 percent of deaths from cancer are in persons older than 65. Moreover, 

research shows that older patients differ from younger patients in their 

susceptibility to disease progression and their response to treatment. 

We also know that current healthcare practices frequently fall short 

of providing the best available early detection, treatment protocols, and quality care for aging patients. Finally, as increasing 

numbers of older people develop cancer, and younger cancer 

survivors live to an older age, the ranks of survivors will grow. The 

difficulties this group will experience include a greater chance of 

developing other health problems, disabling conditions, and 

recurrent cancers. 

All of these factors point to a clear need to continue to 

advance our understanding of the relationships between 

aging and the development and progression of cancer. 

64 The Nation’s Investment in Cancer Research 
Deaths in the United 

States among People 

70.9 71.1 

70.4 72.2 

Colon and Rectum 73.1 80.1 

68.7 79.9 

Urinary Bladder 84.2 88.0 

Stomach 69.4 77.1 

Non-Hodgkin‘s 

38.9 48.6 

Leukemia 68.8 72.6 

Brain 45.4 54.2 

92.5 

58.9 

Ovary 67.2 % Male % Female 

Percent of Cancer 

65 Years and Older 

All Tumor Sites 

Lung & Bronchus 

Pancreas 

Lymphoma 

Prostate 

Breast 

In addition to numerous studies referenced throughout this document, NCI and 

the National Institute on Aging (NIA) have partnered to further invigorate the 

research community’s focus on the intersection of aging and cancer. Two separate 

initiatives, one directed to the scientific community at large and the other to 

NCI-designated Cancer Centers, will support efforts in seven areas of emphasis 

that emerged from the 2001 NCI/NIA Cancer Centers Workshop on Integrating 

Aging and Cancer Research: 

•	 The Biology of Aging and Cancer. Researchers will broaden studies of genetics, 

molecular signatures, age-related changes that contribute to mortality, and 

vulnerability versus resilience in older patients. The work will include studies in 

human biology that reveal which aspects of tumor biology and tumor growth 

vary by age. 

•	 Patterns of Care. Investigators will expand efforts to identify and analyze 

existing and new data from numerous sources, including studies focusing on 

communities, patient management, and specific cancer sites. The goal of these 

patterns of care studies is to determine current cancer care practices and identify where changes are needed to improve the quality of care for older patients. 

•	 Treatment Efficacy and Tolerance. Researchers will focus renewed efforts on 

investigating the effectiveness of available treatments, including radiation 

therapy, surgery, and standard technology; the pharmacology of anti-cancer 

drugs; limitations on admitting older patients to clinical trials; age-related 

treatment outcomes; and methods to prevent or offset unfavorable outcomes 

in older persons. 

•	 The Effects of Comorbidity. New studies will further demonstrate or verify 

effective management of older cancer patients with pre-existing chronic 

conditions and concurrent diseases, including secondary cancers. 

•	 Prevention, Risk Assessment, and Screening. Investigators will increase efforts 

to identify the impediments that prevent older people, both with and without 

symptoms, from receiving preventive, assessment, and screening services. 

•	 Psychosocial Issues and Medical Effects. Researchers will determine the characteristics of early and late effects of treatment, quality cancer care, tumor recurrence, and multiple primary tumors in older patients, and develop interventions 

to improve quality of life, cancer survival, and family and caregiver resources. 

•	 Symptom Management and Palliative Care. Researchers will focus on the 

development of evidence-based interventions and guidelines for the management of pain and other symptoms in patients with cancer, as well as family and 

caregiver support. 

B R O A D R E S E A R C H P R I O R I T I E S : P U B L I C H E A L T H E M P H A S I S 

A Plan and Budget Proposal for Fiscal Year 2005 65 
66 The Nation’s Investment in Cancer Research

NCI’s Challenge Goal of eliminating the suffering and death due to cancer is squarely aligned with the

interests of the 9.6 million cancer survivors in the United States today. While the ultimate goal of eliminating cancer continues to be our long-term commitment, the capacity to dramatically reduce the

suffering caused by cancer is within our immediate grasp. Advances in our ability to detect, treat, and

support cancer patients have turned this disease into one that is chronic or readily managed for

many, and curable for increasing numbers. 

NCI leads the nation in championing research on the health and functioning of our

growing population of cancer survivors. We are learning more about many things:

the nature and scope of problems encountered by young adult survivors of childhood cancer; the differences between younger and older adults in their responses to

treatment; who is at risk for adverse health outcomes; and provocative new interventions for treatment effects such as fatigue, memory difficulties, and pain. To take

advantage of this momentum, we need to advance the science in several areas. NCI

must work with partners to:

• Expand our capacity to track the health and well-being of cancer survivor 

populations and their families or caregivers. 

• Understand the underlying biologic and genetic mechanisms that may increase

survivors’ risk for adverse outcomes. 

• Broaden the scope of interventions development and testing to include the

reduction of cancer-related late morbidity and mortality.

• Explore approaches to promoting optimal posttreatment health behaviors.

• Understand patterns of follow-up care for cancer survivors, including available

community resources to deliver care.

• Communicate our findings to both the survivor and healthcare practitioner

communities. 

The population of cancer survivors continues to grow, a testament to NCI’s many

successes in preventing cancer from progressing to its later and more virulent

stages. These successes include important progress in the delivery and use of cancer

screening; enhancement of early detection technologies; discovery and use of more

effective and often multimodal therapies; provision of a broadening array of 

supportive care and rehabilitative options; and, increasingly, wider adoption of

active screening behaviors and healthier lifestyles by those at risk for cancer, as

well as by those with a history of the disease. Nevertheless, we are also deeply

committed to addressing the needs of, and providing hope for, those living with

and beyond a cancer diagnosis.

PROGRESS IN PURSUIT OF OUR GOAL

Exploring the Genetics of Survivorship 

The recent decoding of the human genome is increasing scientists’ ability to decipher the genetics of survivorship issues, such as hereditary cancer risk patterns that

affect family members and genetic susceptibility to treatment-related late effects.

Researchers will increasingly be able to identify, based on the genetic profile of 

Cancer Survivorship: 

Optimizing Health and Quality of Life after Cancer

Despite the fact that the

majority of survivors (62 

percent) are 5 years or more

posttreatment, few studies

addressed long-term outcomes until NCI began to

sponsor such research, a

direction that is now actively

pursued by the wider 

scientific community.

Research grants that seek 

to evaluate and improve the

posttreatment experience 

of cancer survivors have

increased almost 30 percent

in the last year, including 

a significant focus on 

interventions that improve

psychosocial and healthrelated outcomes. A growing

number of grant applications

(15 percent in Fiscal Year

2002) are being submitted by

investigators new to cancer

survivorship research. 

Discovery 
individual patients, potential therapies that will best treat the cancer while preventing unwanted late effects of treatment. 

For example, the e4 allele of the Apolipoprotein E (apoE) gene has been identified 

as a potential genetic marker for increased risk of neurocognitive deficits among 

adult survivors of cancer (breast and lymphoma) who have undergone chemotherapy. 

NCI is funding research to investigate mechanisms of risk for these late effects using 

noninvasive techniques such as morphometric magnetic resonance imaging (MRI), 

functional MRI, diffusion tensor imaging, MR spectroscopy, and positron emission 

tomography. 

Exploring the Impact of Cancer on the Family 

As cancer care migrates into the outpatient setting, the economic, physical, and 

emotional burden on family members is increasing. NCI needs to explore the 

impact on family members affected by this illness, many of whom may themselves 

be at increased risk for cancer due to shared cancer-causing genes, lifestyle choices, 

and/or toxic exposures. Over the next several years, NCI will collect populationbased data on the impact of major cancers on U.S. families of diverse racial/ethnic 

and socioeconomic backgrounds. This survey will generate basic descriptive statistics on the percentage of family households with cancer survivors and caregivers, by 

demographic characteristics. In addition, the survey will provide data on the medical, familial, psychosocial, and economic factors that may affect family outcomes. 

The data will be made available to researchers and program planners to monitor 

the success of interventions and educational resources. 

Expanding Research Addressing Underrepresented/Underserved Survivors 

In September 2002, NCI convened a meeting to address survivorship issues in 

minority and medically underserved survivor populations. Held in conjunction with 

the semiannual board meeting of the Intercultural Cancer Council, the meeting provided an opportunity to discuss research challenges and solutions. Participants 

reached a consensus on recommendations for collaboration between academic 

research centers and community organizations, including guidelines for research 

studies and successful subject recruitment. 

The Cancer Disparities Research Partnership (CDRP) program will support 5-year 

cooperative agreements to investigate survivorship in underserved patient populations in locations where health disparities exist. The first two awards were given to 

sites serving Native American and Hispanic populations. Four additional sites will 

receive funding in 2003. 

Understanding Research Gaps 

A review of survivorship research of underserved populations identified only 65 

studies with sample sizes sufficient to permit detailed comparisons among diverse 

groups. Populations requiring further study include diverse ethnic groups, those 

diagnosed at age 65 or older, rural populations, low-income groups, those with 

limited education, and survivors with less commonly studied types of cancer. 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 67 
Discovering Long-Term and Late Effects 

The Common Terminology Criteria for Adverse Events represents the first comprehensive, multimodality grading system for reporting the incidence of both acute and 

late effects of cancer treatment, as well as their duration. Educational tools will be 

made available to the scientific community. This new scoring system will enable 

investigators to compare newer treatments for all cancers with the current regimens; 

investigate molecular mechanisms for late tissue damage based on the severity of 

effects experienced by patients; facilitate the development of interventions for use in 

clinical trials to prevent, reduce, or possibly reverse late effects of cancer treatment; 

and permit the standardized reporting of adverse events and of comparisons of 

outcomes between trials and institutions. 

Development Delivering Best Practices through Partnerships and Consensus Building 

Many Cancer Centers and academic institutions have developed specialized follow-up 

care clinics and programs for survivors of childhood cancer. In the adult arena, a range 

of models are being used for follow-up care for survivors in Cancer Centers, community oncology practices, and primary care settings. However, there has been little consensus about what constitutes optimal care, no coordination of efforts to deliver such 

care, and no attempts to evaluate program effectiveness, specifically the impact of 

such programs on survivor outcomes and the cost of care. NCI is bringing people 

together to focus on the problem through initiatives such as the following: 

•	 NCI, in collaboration with the American Cancer Society, established a Biennial 

Cancer Survivorship Conference, inaugurated in June 2002. The papers from 

this conference addressed such topics as cancer survivorship and aging; 

promoting posttreatment adaptation; pathways to psychosocial care; family 

outcomes; and improving survival in the setting of advanced disease. Designed 

to bring the consumer’s voice to the scientific proceedings, the meeting was 

attended by more than 100 cancer survivors. 

•	 Two International Workshops on Long-Term Follow-Up Care Programs for 

Survivors of Pediatric Cancer were convened to formulate a research agenda 

and establish a working group to advance the science of follow-up care by identifying and examining the efficacy of models for posttreatment care; determining the optimal frequency, content, setting, and provider for such care; developing best practices for follow-up care for both pediatric and adult survivors; 

and creating a database on survivor care and outcomes across follow-up programs and clinics. 

•	 A National Institutes of Health state-of-the-science meeting, Symptom Management 

in Cancer: Pain, Depression, and Fatigue, identified key gaps in our knowledge 

and delivery of state-of-the-art palliative care, including recognition that pain is 

often undertreated, despite the availability of effective interventions; cancer-related 

depression and fatigue are extremely common and have a profound impact on a 

patient’s well-being; insufficient resources are allocated to studying the occurrence, causes of, and impediments to effective treatments for these symptoms; 

and healthcare professionals, caregivers, and patients need to focus on symptom 

management throughout the course of cancer. (See also page 55.) 

68 The Nation’s Investment in Cancer Research 
The NCI-supported Childhood Cancer Survivor Study is a cohort of over 14,000 

the University of Minnesota and includes 27 participating centers in the United States and Canada. 

• 

• 

• 

to their siblings. 

• 

• 

that survivors will need special-education services. 

• 

• 

Childhood Cancer 

Survivor Study Informs 

Intervention Development 

5-year survivors of childhood cancer — the largest and most extensively characterized group of childhood survivors in North America. This cohort is a unique resource 

for addressing issues faced by the ever-growing population of childhood survivors, 

including risk of second cancers; adverse endocrine, reproductive, and psychosocial 

outcomes; and cardiopulmonary problems. A model of collaboration, the study is coordinated by researchers at 

Significant findings from the Childhood Cancer Survivor Study include the following: 

Many adult survivors of childhood cancer cannot recall basic aspects of their diagnosis and treatment, 

which could impair their ability to seek and receive long-term follow-up care. 

Childhood survivors are at increased risk for developing second cancers, but the degree of risk varies 

markedly by initial cancer diagnosis and treatment. Associated risk factors include an initial diagnosis of 

Hodgkin’s disease or soft-tissue sarcoma, younger age at diagnosis, and certain types of chemotherapy. 

Survivors of childhood leukemia and lymphoma have a somewhat increased risk for depression compared 

Most chemotherapy treatments do not lead to pregnancy problems, but women who received radiation to 

the pelvis during childhood are more likely to have low birthweight babies. 

Radiation to the brain during childhood, especially at high dosages, is associated with an increased likelihood 

Survivors of childhood leukemia and lymphoma who received high doses of radiation to the brain are at 

increased risk for obesity. 

When compared to the U.S. population, childhood survivors are less likely to smoke. If they do smoke, they 

are more likely to quit. Even so, the rate of smoking among study participants is far too high: 28 percent 

are smokers or former smokers. 

Delivery 

We must ensure that sufficient numbers of investigators and clinicians are committed to understanding and 

caring for cancer survivors. 

Continued training opportunities assist clinicians with 

acquiring the knowledge and 

skills necessary to keep pace 

with the rapidly changing 

needs of tomorrow’s cancer 

survivors. 

Disseminating Research Findings: Communication Tools and Resources 

NCI has created several products that enable us to more accurately track who is 

surviving cancer and to communicate more effectively with diverse audiences: 

•	 The Prevalence Statistics Website provides updated information about cancer 

survivors in the United States. The site will be expanded to track minorities and 

to provide information on survivors’ second malignancies, quality of life, and 

prevalence data by state. 

•	 The Facing Forward series for cancer survivors, family members, and medical 

professionals is designed to educate and empower cancer survivors as they face 

the challenges associated with life after cancer treatment. 

•	 In partnership with Cancer Care, the Intercultural Cancer Council, the Lance 

Armstrong Foundation (LAF), and Living beyond Breast Cancer, NCI created a 

three-part teleconference series to provide survivors and their loved ones with a 

better understanding of what to expect after treatment ends. 

•	 The NCI Cancer Survivorship Website (dccps.cancer.gov/ocs) is a comprehensive

resource for researchers, advocates, cancer survivors, and the public. 

BROAD RESEARCH PRIORITIES: PUBLIC HEA L TH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 69 
CANCER SURVIVORSHIP: 

OPTIMIZING HEALTH AND QUALITY OF LIFE AFTER CANCER 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Reduce the adverse Discovery 

effects of cancer 1. Expand research efforts to understand the biological, physical, psychological, 

diagnosis and treat- and social mechanisms, and their interactions, that affect a cancer patient's 

ment, and improve response to disease, treatment, and recovery. $12.75 M 

health-related out- ■ Support investigators with access to extant cohort and case-control studies that include cancer 

comes for cancer survivor populations to leverage these databases through collaborative efforts. $0.25 M 

survivors and their 

families. 

■ Conduct behavioral and epidemiological studies of cancer and its treatment on survivors who are 

posttreatment, by examining both negative and positive physiologic and psychosocial effects, and 

their correlates. $5.00 M 

■ Continue to support Long-Term Cancer Survivor studies and the associated investigator working 

group. $4.00 M 

■ Identify the genetic and/or phenotypic markers of susceptibility to treatment-related adverse effects 

and gene-environment interactions, using molecular epidemiological research. Expand understanding of the biologic and physiologic mechanisms in the adverse chronic and late effects of current and new cancer treatments. $3.00 M 

■ Synthesize the research with respect to the role of sociocultural, behavioral, emotional, and spiritual factors in survivor and family outcomes and survivor’s willingness to adopt appropriate surveillance and health maintenance behaviors posttreatment. $0.50 M 

2. Expand the development and use of tools to assess the health-related quality 

of life and quality of care of posttreatment cancer survivors and their family 

members, as well as NCI’s capacity to track outcomes for these populations. $5.00 M 

■ Promote the testing and routine use of instruments to assess health-related quality of life beyond 

the active treatment period. Include efforts to accelerate the adoption of newly established common toxicity criteria for late effects of cancer treatment. $2.00 M 

■ Develop measures to evaluate comorbidities that are both cancer- and noncancer-related, in 

collaboration with other NIH institutes (e.g., National Institute on Aging; National Heart, Lung, and 

Blood Institute). $1.50 M 

■ Conduct national surveys of physicians and survivors of pediatric and adult cancer regarding followup care. $1.50 M 

■ Assess the health-related information needs and resources of cancer survivors through the Health 

Information and National Trends Survey (HINTS). (See page 102.) 

70 The Nation’s Investment in Cancer Research 
Development 

3.	 Accelerate intervention research in order to reduce cancer-related chronic or 

late morbidity and mortality. $9.00 M 

■ Expand research on the most promising and cost-effective interventions to address cancer survivor 

needs for improved quality of life — e.g., reducing cancer-related symptoms such as distress, pain, 

and nausea; minimizing posttreatment organ dysfunction; treating infertility; promoting healthy practices such as exercise, smoking cessation, and diet change; and addressing individual needs. This 

research includes investigating the impact of well-characterized and controlled interventions (type, 

intensity, and length) on appropriate intermediate biomarkers — e.g., immune functioning, cortisol 

levels, PSA levels. $5.00 M 

■ Develop interventions that promote the health and well-being of family members or caregivers as 

well as interventions that target minority and medically underserved populations. $2.00 M 

■ Develop screening tools that identify individuals who are at high risk for poor outcomes, and assess 

the impact of such screening on patterns and outcomes of care. $2.00 M 

Development and Delivery 

4.	 Ensure the delivery to relevant audiences of new information, interventions, 

and best practices, in collaboration with other Federal and health- or cancerrelated professional and nonprofit organizations. $3.00 M 

■ Develop and disseminate best practice guidelines for follow-up care, surveillance, and monitoring of 

cancer survivors who have completed initial cancer treatment. $1.00 M 

■ Study the adoption and impact of best practices in posttreatment care. $1.50 M 

■ Develop and disseminate curricula and standards for the delivery of effective psychosocial and 

supportive care across the illness continuum. $0.50 M 

■ Develop and disseminate educational materials for family members and healthcare providers of 

cancer survivors. 

Management and Support $ 0.50 M 

Total $30.25 M 

BROAD RESEARCH PRIORITIES: PUBLIC HEALTH EMPHASIS 

A Plan and Budget Proposal for Fiscal Year 2005 71 
Platforms for Discovery, Development, and Delivery: 

Building Synergy through Interdisciplinary Team Science 

Bringing the benefits of cancer research to the American people depends on building and sustaining the 

strong research mechanisms, support structures, and collaborations that make it possible for us to pursue 

rapidly evolving discoveries. NCI must provide the vision, creative environment, and diverse resources needed to ensure a fast paced and synergistic flow of innovative thinking among scientists in disparate scientific 

disciplines. We must also leverage our collaborations with other government agencies, academia, and industry, 

focusing on steering major breakthroughs toward the delivery of effective cancer interventions. 

Investigator-Initiated Research builds on the synergism at medical schools, hospitals, universities, and research centers for asking the critical questions, exploring the 

options, and developing and testing innovative technologies. Centers, Networks, 

and Consortia created and supported by NCI comprise a model framework in 

which investigators can work effectively in teams, collaborate for progress, and 

ensure that results advance from discovery to intervention development and delivery. 

NCI-supported Clinical Trials provide the crucial infrastructure for moving new 

cancer interventions from the laboratory to studies in people with, or at risk for, 

cancer and then to the healthcare setting. NCI’s Intramural Research Program, 

which complements our robust Extramural Research Program, also provides a 

unique venue for innovative investigation, as well as translation, and application of 

research findings. 

We must continue to use these platforms to build and enhance a research system 

that will allow and encourage the scientific community to share and apply new 

discoveries and emerging technologies. We need new funding arrangements that 

will promote and reward innovative thinking; speed cross fertilization of ideas 

across scientific disciplines; facilitate collaborations among government, academia, and industry; and bring advances in cancer care to all populations. And we 

need to foster and coordinate efforts that would be too large for the individual 

investigator by promoting team endeavors and encouraging scientific integration 

without inhibiting individual creativity. 

To streamline progress for cancer in as many ways as possible, we need to: 

•	 Guide, support, and leverage the work of the individual investigator and that 

performed within NCI-supported Cancer Centers, networks, and consortia. 

•	 Maximize physician and patient access to clinical trials for prevention, diagnostic, and therapeutic interventions. 

•	 Train top researchers in oncology and arm them with the finest technologies 

and tools available. 

•	 Build and sustain the interdisciplinary connections so vital to 21st century science. 

72 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 73

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY

Investigator-initiated research — research independently conceived and developed by scientists —

has always been the primary means by which biomedical research is funded and conducted. Driven by

the synergism at medical schools, hospitals, universities, and research centers, these investigators 

ask the critical questions, explore the options, develop and test innovative technologies, and make the

discoveries that lead to better cancer science and its application to patient care. 

Providing Resources to Maximize Investigator Productivity

Science is changing rapidly, and the promise and problems of research are changing

along with it. In many areas, a single laboratory can easily accomplish goals that

would have been unapproachable only a few years ago. This is due to the availability of vast amounts of information as well as new tools and techniques for

analysis. The genetic makeup of cells and tissues, as well as complex gene expression patterns, can be analyzed in exquisite detail, and methods to analyze proteins

and other cellular components are developing rapidly. Methods for discovering and

analyzing promising drugs aimed at cancer-causing pathways have outfitted scientists with an arsenal of research approaches and technologies more comprehensive

than any previously available. 

Although new research tools increase productivity, their costs place an extra burden

on grant budgets, threatening to decrease the number of grants that can be supported. The increasing complexity of research projects demands that researchers work

in an interdisciplinary team environment, rather than in isolated laboratories with

occasional collaborators. NCI is striving to ensure that the resources needed for

maximum productivity are widely available and that the support mechanisms facilitate, rather than hinder, the kind of research that can and should be done.

Balancing Research Opportunities and Costs

NCI has seen an enormous increase in the funding needed to allow scientists to fully

exploit new technologies and approaches to conducting research. In Fiscal Year

2003, for example, the number of applications submitted to NCI increased by 9 percent, and the total NCI spending on research projects was nearly 8 percent higher

than the year before. This cost increase reflects a larger number of total active awards

as well as some growth in the average cost of awards. While we expect this trend to

moderate, we must balance the growing number of research opportunities with the

rising costs of research. Reviewer assessments of research applications consistently

identify the top 35 percent to 40 percent of grants as highly meritorious; the proportion actually funded (the success rate) has averaged 26 percent in recent years. To

maintain this success rate, NCI carefully reviews individually approved grant applications for programmatic efficiencies, reducing the cost of a grant by an average of

10 percent. In addition to leveraging our Federal dollars, we must ask researchers to

complement this funding from other sources as much as possible.

For the next generation of scientists to choose to enter cancer research, they must perceive opportunities for discovery with the potential to change our world. A sufficient

infusion of resources and funding into investigator-initiated research will help to

ensure that science students, as well as current researchers, undertake cancer research.

Enhancing Investigator-Initiated Research 

Investigator-initiated research

is the principal means by

which scientists address 

high-priority goals, such as

those identified by the

Progress Review Groups

focused on specific types of

cancer. It is also a mainstay

for cancer research training

and for enabling multidisciplinary collaboration. 
PROGRESS IN PURSUIT OF OUR GOAL 

NCI supports and Identifying and Supporting High-Priority Research


fosters investigator- NCI takes extra steps to identify and support high-priority research by:
 initiated research through • Seeking out and supporting compelling research proposals with exceptions
 a variety of policy 


decisions and flexible funding, particularly projects that employ dramatically new or unconventional


funding options. 	 approaches to understanding cancer. 

•	 Giving special consideration to proposals responsive to high-priority research 

areas identified by NCI advisory groups, NCI Program Announcements of priority research areas, and recommendations from Progress Review Groups (PRGs) 

for research related to specific cancers. 

We are also exploring better ways to define and promote the exploration of 

uncharted areas of research and to give them heightened consideration when 

reviewing grant applications. 

a later date or performing a colposcopy (examination of the cervix with a special magnifimodels to accurately distinguish between normal and neoplastic tissue. 

Cervical Cancer 

Computer analysis of 

the cervix 

NCI-supported scientists are developing a noninvasive test for the screening of cervical 

neoplasia (abnormal and uncontrolled cell growth). Preliminary testing suggests that this 

screening method may be more accurate, as well as more acceptable to patients, than 

standard methods. The current standard of care calls for screening to begin with a routine 

Pap smear. If the results are abnormal, the physician may recommend repeating the test at 

cation tool) and/or biopsy, depending on the specific results and patient history. 

NCI-supported basic and clinical researchers are assessing emerging imaging technologies that use fluorescence and reflectance spectroscopy to noninvasively detect cervical 

neoplasia. Basic scientists have demonstrated that this imaging approach accurately 

detects the intracellular changes that occur as cells progress from a normal to a neoplastic 

state. The scientists have also made major progress in understanding the biological basis 

of cervical tissue fluorescence and have applied this knowledge to develop mathematical 

Scientists recently carried out clinical trials showing that the imaging techniques are feasible for use in large populations. For example, one team experimented with using different wavelengths of fluorescent light 

to design relatively simple, inexpensive imaging systems for use in screening trials worldwide. Another team showed that 

fluorescence and reflectance spectroscopy can be used anytime during the menstrual cycle except during menstruation. 

Participants in this trial reported significantly less pain and anxiety and were more satisfied with spectroscopy than with the 

usual care procedures. NCI investigators will continue to develop this promising new technology in a large randomized trial 

comparing fluorescence and reflectance screening with standard cervical cancer screening techniques. 

Imaging Researchers 

Develop Promising 

Screening Technique 

fluorescence and reflectance 

spectroscopic imaging of 

74 The Nation’s Investment in Cancer Research 
delivery continuum. 

that this conception understates the potential benefits of this therapeutic intervention. 

transplant strategies, including the use of donor leukocyte (white blood cell) 

Discovery-DevelopmentDelivery Continuum 

Investigator-initiated research is the engine of scientific discovery. It is also much 

more. Bone-marrow transplantation research, traditionally carried out under investigator-initiated program projects and traditional (R01) research grants, is an excellent 

example of cancer intervention research that spans the discovery-developmentOver the past 15 years, a number of outstanding research groups have produced a 

quiet revolution in this field. In cancer therapy, bone marrow (or peripheral stem cell) 

transplantation was originally viewed largely as a supportive therapy that would allow 

the use of larger, more effective doses of chemotherapy and radiation. It is now clear 

In transplants from related donors, where transplantation has been most effective in 

leukemias and lymphomas, much of the benefit derives from an immune response of 

donor white blood cells against residual tumor cells. This recognition has led to new 

infusions for the treatment of relapse. Preparative regimens for both donors and recipients have been modified to maximize the immune-mediated benefit, improving efficacy while greatly reducing the toxicity in the recipient. As a result, the treatment is now available to older patients, 

extending the number of people who can benefit. Moreover, the focus on immune cell reactivity to cancer has provided important new directions for pursuit of immunotherapeutic strategies outside the transplant setting. 

Ultimately, all research progress stems from the creativity and drive of the cancer research community. NCI maintains a balanced portfolio of diverse support mechanisms to maximize the progress achieved through a remarkably 

wide range of investigational approaches. Within this portfolio, investigator-initiated research remains critical not 

only to discovery, but also to the development and delivery of cancer interventions. 

Investigator-Initiated 

Research in Bone Marrow 

Transplantation Spans the 

 D E V E L O P M E N T, A N D D E L I V E R Y 

Maximizing the Ability to Start New Projects and Collaborations 

NCI maximizes the pace of research by providing a broad range of flexible funding 

options and promoting collaborations and resource sharing wherever possible. NCI is: 

•	 Providing opportunities for collaborative study through awards such as program 

project grants (P01s) and cooperative agreements, in addition to the traditional 

research project grants (R01s) that make up the bulk of NCI’s research portfolio. 

•	 Providing seed funds for promising research. In Fiscal Year 2002, the number 

of small (R03) and exploratory/developmental (R21, R33) grants awarded 

increased more than 17 percent over the previous year. 

•	 Enabling investigators to take advantage of unanticipated opportunities or to 

pursue interdisciplinary collaborations with administrative supplement funds. 

For example, through NCI’s Activities to Promote Research Collaborations 

Program, grantees request funding for collaborations that will pursue novel, 

unforeseen opportunities and embrace resource sharing; develop new technologies; or organize cross-disciplinary meetings or workshops. 

•	 Promoting collaborative studies and sharing of resources through innovative 

networks and consortia. 

PLAT F O R M S F O R D I S C O V E R Y,

A Plan and Budget Proposal for Fiscal Year 2005	 75 
ENHANCING INVESTIGATOR-INITIATED RESEARCH 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Accelerate 1. Accelerate the pace of discovery through increased funding for, and greater 

discoveries and numbers of, competing research grants. 

their application ■ Move research projects toward funding at the full levels recommended by peer reviewers. 

by expanding 

■ Fund, at a minimum, 35 percent of competing applications, with the following areas of emphasis: and facilitating (1) the highest scientific merit; (2) a less certain probability of success, but potential to yield greater researcher access reward if they do succeed; (3) unconventional approaches but unique promise; (4) a focus on areas 

to resources and of extraordinary need in specific fields of investigation or model systems; and/or (5) the involvement 

new technologies. of new investigators. 

2. Facilitate rapid movement from discovery to development to delivery by using 

established mechanisms and creating novel special awards to encourage 

transdisciplinary and collaborative research. 

■ Expand supplemental funding for grants to promote new interdisciplinary collaborations for bringing 

together basic, clinical, and population scientists, such as those fostered by NCI’s Activities to 

Promote Research Collaborations Program. 

■ Expand researcher access to central resources, such as databases, tissue banks, and animal models, 

by using funding supplements; centers, networks, and consortia; and cooperative resource programs. 

■ Expand researcher access to: (1) technologies that promote interdisciplinary research and collaborations, and (2) the expertise needed to move discoveries to application. 

■ Develop and make available information technology tools to foster and enhance interdisciplinary 

communication and collaboration. 

■ Expand the funding for collaborative research awards, such as program project grants and cooperative agreements, for consortia that facilitate translational research. 

■ Encourage more patient- and population-based research by expanding the use of exploratory grants. 

Enabling Research Across the Discovery-Development-Delivery Continuum 

The undirected nature of investigator-initiated research requires grant mechanisms with substantial flexibility. Investigators use this flexibility to carry out development projects, all the 

way to and through Phase III clinical trials. (See page 75.) While researchers supported by 

investigator-initiated grants do not have immediate access to specialized resources provided 

by NCI under such targeted mechanisms as the Cooperative Group clinical trials program or 

SPOREs, informal alliances are encouraged by NCI staff and can be particularly beneficial 

for research carried out at NCI-supported Cancer Centers. 

76 The Nation’s Investment in Cancer Research 
3.	 Encourage investigators from a variety of scientific backgrounds to commit to 

careers in cancer research and to propose more innovative and higher-reward 

projects. 

■ Continue to allocate the first 80 percent to 90 percent of available funds for research project grants 

through the well-established peer review selection process, while ensuring that proposals from new 

investigators are also funded at a rate comparable to those of more established investigators, 

utilizing exceptions as necessary. 

■ Use a special administrative evaluation process to fund particularly innovative and potentially 

high-reward projects. 

4.	 Encourage investigation in priority areas identified by advisory committees, 

NCI staff, Progress Review Groups (PRGs), and other groups, through regular 

and special award mechanisms. Leverage resources for these efforts through 

collaborative initiatives. 

■ Monitor investigator-initiated research to assess whether these projects alone are meeting 

programmatic objectives, such as those identified in specific disease areas. 

■ Set aside 10 to 15 percent of funds for Requests for Applications in specifically targeted areas 

of need. 

■ Support Program Announcements and investigator-initiated projects that target identified gaps 

and/or emerging opportunities (e.g., those identified by the PRGs and other priority setting and 

strategic planning activities). 

■ Enhance coordination within and among initiatives, and increase management and support 

commensurate with the growth of the portfolio. 

■ Encourage outreach to establish public-private partnerships and to leverage current NCI-funded 

activities with new, complementary, non-NCI sources of support, through supplemental awards. 

Management and Support $ 0.80 M 

Total $123.50 M 

Training Scientists for Cancer Research 

By providing salary support on research grants, investigator-initiated research is now the single largest training support mechanism for scientists. Training programs are critical, but have 

not expanded as rapidly as other grant mechanisms.To compensate, trainees are increasingly 

supported directly on grant budgets. In addition, the special attention accorded to research 

grants to new investigators eases their transition to independent research careers. 

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

A Plan and Budget Proposal for Fiscal Year 2005 77 
78 The Nation’s Investment in Cancer Research

Researchers face distinct obstacles to the development of new treatments for cancer in children. 

For example:

• Even cancers that are common in children are rare compared to most adult

malignancies. Accumulating enough cases to test a new treatment requires collaboration among multiple research organizations. Also, drug development costs

for targeting pediatric tumors can be prohibitive for the pharmaceutical industry.

• Studies in children pose unique risks to drug developers because the discovery of

adverse events in children could jeopardize the potential for FDA approval of the

same or similar drugs for adults. 

• Twenty-first century anti-neoplastic drug development often focuses on agents

that target specific molecular alterations in tumor cells. Therefore, drugs developed for adult cancers may have little or no applicability to pediatric cancers

because of differences in their molecular pathology. 

NCI is addressing these obstacles through a research strategy focused on the development of new treatments

for pediatric cancers — treatments that are not a by-product of drug development for adults. The new strategy spans the spectrum from preclinical drug discovery through Phase III studies aimed at obtaining FDA

approval. For example: 

• The newly established Pediatric Preclinical Testing Program aims to annually

screen 10 to 15 new agents, or combinations of agents, against a panel of preclinical models for common pediatric tumors (e.g., mouse models). In this way,

researchers can rapidly identify agents with activity against pediatric tumors.

These preclinical models will also allow researchers to screen cancer drugs developed for adults for their potential applicability to pediatric tumors.

• NCI’s Pediatric Oncology Preclinical Protein-Tissue Array Project (POPP-TAP)

and the Children’s Oncology Group Phase I Consortium are characterizing the

molecular features (RNA and protein expression) of pediatric tumors in children

and in corresponding preclinical models. This information will help preclinical

researchers to select the model that most resembles the childhood cancer under

study. Molecular characterization of preclinical tumor models will also point to

critical signaling pathways that can be targeted by specific anti-cancer agents. 

• NCI-funded Cooperative Groups have successfully brought together pediatric

oncologists worldwide to enroll children with cancer into clinical trials. This

international cooperation allows oncologists to learn from each case and to

accomplish the kind of high quality clinical research that most effectively assesses the safety and efficacy of experimental treatments. 

NCI is committed to surmounting current obstacles through focused discovery initiatives that ensure children are not left behind — that they survive cancer through

tailored, safe, and effective treatment. 

NCI Addresses Obstacles to the Development of

New Treatments for Pediatric Cancer
The centers, networks, and consortia created and supported by NCI over the past 10 years comprise a model

framework in which investigators can work effectively in teams, collaborate for progress, and ensure that

results advance from discovery to intervention development and delivery. 

• NCI-designated Cancer Centers1 are highly effective platforms that span the

discovery-development-delivery continuum. These Centers organize and integrate multidisciplinary research across departments and schools within a single

institution or consortium of local institutions. Emphasizing the cancers that represent the greatest health threat to their communities, NCI-designated Cancer

Centers provide scientists with the most advanced technologies and promote

new research opportunities; work collaboratively with industry; perform 

state-of-the-art translational research; and conduct education, outreach, and

information programs. NCI-designated Cancer Centers are highly effective at

leveraging additional resources for cancer research and education from organizations in the public as well as private sectors.

• NCI Centers of Excellence, usually evolving within Cancer Centers, connect

specialized groups of scientists in collaborative, interdisciplinary research.

Projects are closely integrated with the efforts of other centers of excellence,

research networks and consortia, and institutions throughout the Nation. NCI

Centers of Research Excellence are usually devoted to discovery and development of new interventions and are often linked to private industry.

• Networks and consortia are geographically dispersed multidisciplinary groups

whose goals require inter-institutional collaborations. Networks and consortia

usually focus on the development or validation of new interventions, ranging

from new therapies to genetic risk counseling to outreach.

Embracing an Evolving Paradigm in Cancer Research

This infrastructure is now poised to exploit an evolving paradigm in cancer research

that will help attain NCI’s Challenge Goal of eliminating the suffering and death

due to cancer. To move forward, by realigning existing resources and incorporating

new ones, NCI must: 

• Employ progressive bioinformatics and communication systems.

• Encourage collaborative, multidisciplinary research, and require integration

and sharing of results.

• Realize economies of scale, avoid duplications, and exercise regional sharing.

• Promote growth in strategic areas of research and technology development.

• Strategically broaden the geographic impact of the centers, networks, and 

consortia.

• Improve the access of minority and underserved populations to state-of-the-art

research and resources.

• Create and strengthen partnerships with government agencies and community

organizations. 

• Broadly provide expertise, facilities, and other resources to caregivers, patients

and families, and appropriate health agencies.

A Plan and Budget Proposal for Fiscal Year 2005 79

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY

Transforming the Capacity of Centers, Networks, and Consortia 

The interdisciplinary nature 

of today’s cancer research

requires new infrastructures

that support team science

and enable the sharing of a

multitude of resources. 

The new research paradigm

hinges on interdisciplinary

science, strategic partnerships, immediate application

of new technologies, optimal

information sharing, and

close links to health delivery

systems. 

1 In this document, “NCI-designated Cancer Centers” is sometimes abbreviated as “Cancer Centers.” 
PROGRESS IN PURSUIT OF OUR GOAL


NCI is strengthening the 

capacity of NCI-designated 

Cancer Centers to audit 

research, ensure data safety, 

and monitor human 

research. A broad new 

NCI bioinformatics initiative 

will pave the way for investigators at NCI-designated 

Cancer Centers to participate 

in a national network for 

collaborative research and 

sharing of research results, 

while ensuring the safety of 

patients and populations. 

(See page 96.) 

Strategic Expansion of NCI’s Centers, Networks, and Consortia 

NCI-designated Cancer Centers are now present in 31 states and the District of 

Columbia, and NCI has planning grants in place for developing Cancer Centers in 

another five states. NCI is actively working with institutions in five additional states 

that have the capability to develop strong research and outreach programs, with the 

goal of creating a Cancer Centers program that benefits the entire Nation. NCI is 

also creating new Cancer Center models to serve states that do not have the institutional infrastructure to sustain a more traditional NCI Cancer Center. These innovative models will address geographic expansion, education and outreach activities, 

partnerships for research and delivery, and aids for underserved populations. For 

example, Cancer Centers are now engaged in a unique partnership, Overcoming 

Barriers to Early Phase Clinical Trials, with several major pharmaceutical companies. 

Specialized Programs of Research Excellence (SPOREs), the original Centers of Excellence 

created by NCI in 1992, focus entirely on discovery-to-delivery research dedicated to specific cancers. There are now 50 SPOREs in place across the Nation, with all major cancer 

sites represented. These SPOREs are poised to rapidly conduct early-phase clinical studies, 

sharing information via a protected Web-based system. The SPOREs effectively work 

together across institutional boundaries and have begun productive collaborations with 

NCI networks and consortia, as well as through public-private partnerships. For example, 

a partnership with the Avon Foundation has generated over 15 early-phase clinical trials 

in breast cancer. A new supplement program for early-phase trials in all cancer sites is also 

working well. Fifteen new early-phase clinical trials are ongoing in the longest-standing 

This includes most medical institutions in the United States with major biomedical 

Cancer Centers Speed 

Benefits to Cancer 

Patients and 

Risk for Cancer 

NCI-supported Cancer Centers, networks, and consortia are natural hubs for national 

leadership in the war against cancer. They also provide a means for fostering coalitions 

and partnerships with other cancer funding organizations, professional societies, businesses, industry, communities, and local and state governments. NCI’s leadership will 

accelerate the pace of delivery of effective cancer interventions to the public. 

NCI-designated Cancer Centers will be particularly important in future strategies to 

improve the delivery of new state-of-the-art interventions to the public. In the last 5 years, 

more than 40 of the 60 Cancer Centers have received the “comprehensive” designation. 

research programs. Directors and investigators at these Comprehensive Cancer Centers 

participate with NCI in outreach activities in order to speed the benefits of research to 

patients, physicians and other caregivers, and communities, especially to those in underrepresented geographic regions of the Nation. 

the Delivery of Research 

To Populations at 

80 The Nation’s Investment in Cancer Research 
include the following: 

• 

• 

• 

• 

• 

• 

• 

• 

National Cancer Advisory 

Confirms Central Role of 

Cancer Centers and 

SPOREs in Delivery of 

Cancer Interventions 

In 2003, the National Cancer Advisory Board completed a report of an ad hoc working group 

charged with establishing a blueprint for NCI-designated Cancer Centers and Specialized 

Programs of Research Excellence (SPOREs). The report confirmed the central role of Cancer 

Centers and SPOREs in future strategies for improving the delivery of cancer interventions. 

The report lists recommended strategies for balancing the breadth and depth of these programs, maximizing translation of research discoveries, developing objectives for a national 

cancer agenda focused on reducing the cancer burden, and facilitating partnerships with 

other governmental, private, philanthropic, and business entities. Specific recommendations 

Consolidate shared resources in Cancer Centers to create greater economies of scale. 

Look to Cancer Centers for piloting new research, education, dissemination, and delivery strategies. 

Provide greater support for critical activities such as tissue banks, clinical data management and safety, and conformance to regulatory requirements. 

Encourage greater geographic distribution of Cancer Centers by creating programs for institutions that cannot currently 

meet all the requirements of the more research-intensive institutions that are currently supported by NCI. 

Provide the means for Cancer Centers to actively establish strategic, programmatic links with state health departments, 

other state agencies, local governments, and Federal agencies such as the Centers for Disease Control and Prevention. 

Encourage Centers to develop the infrastructure to test and implement novel methods for disseminating new knowledge 

in clinical, cancer control, and early detection research. 

Adopt as a top priority an integrated clinical research informatics system that will serve Centers and industry. 

Work with the Federal Office of Human Research Protections to engage Institutional Review Boards to develop a 

centralized review of multicenter trials. 

Many of these recommendations are reflected in NCI’s ongoing programs and plans for centers, networks, and consortia. 

The report will be a valuable resource to NCI in its continued strategic planning. 

Board Working Group 

 D E V E L O P M E N T , A N D D E L I V E R Y 

SPOREs, focusing on prostate, gastrointestinal, and lung cancers. These achievements mark 

the end of the rapid expansion phase of the SPOREs and a transition to strategic growth. 

Other Centers of Excellence founded on the SPOREs model are spearheading interdisciplinary research in a number of specialty areas. For example: 

•	 The Transdisciplinary Tobacco Use Research Centers (TTURCs) support a 

broad array of studies related to tobacco use, including genetic and behavioral 

research. (See page 39.) 

•	 In Vivo Cellular and Molecular Imaging Centers bring together experts from 

diverse scientific and technological backgrounds to conduct research on cellular and molecular imaging in cancer. (See pages 31-32.) 

•	 Interdisciplinary Research Teams for Molecular Target Assessment study critical biological processes to uncover high-priority targets for cancer intervention 

strategies. (See page 26.) 

•	 Centers of Excellence in Cancer Communications Research focus on advancement of cancer communication science. (See page 99.) 

•	 Centers for Population Health and Health Disparities research the interaction 

of social, cultural, and physical environmental determinants of cancer incidence 

and outcomes, and the behavioral and biologic factors that contribute to them. 

(See page 59.) 

A Plan and Budget Proposal for Fiscal Year 2005	 81 

P L A T F O R M S F O R D I S C O V E R Y,
TRANSFORMING THE CAPACITY OF CENTERS, NETWORKS, AND CONSORTIA 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Integrate research 1. Promote strategic growth of the NCI Cancer Centers, incorporating and 

infrastructures and realigning resources to accelerate discovery, development, and delivery of 

collaborations that cancer interventions. $27.50 M 

enable multiple scien- ■ Develop regional strategies for maximizing the impact of NCI Cancer Centers. $0.50 M 

tific disciplines to ■ Deploy new Cancer Center consortium models to two regions of the country in which no single insti­ address large prob- tution has the research strength to become an NCI-designated Cancer Center. $3.00 M 

lems in human cancer 

■ Develop Research Enhancement and Cancer Health (REACH) programs that will draw more institu­ that cannot be solved tions into a collaborative network with NCI Cancer Centers, promote partnerships with local com­ by individual investi- munities to disseminate research benefits, and influence more rapid delivery of state-of-the-art cangators. Promote net- cer prevention and treatment. $5.00 M 

works, partnerships, ■ Develop and implement state Cancer Plans and improve public health practice for the prevention, and coalitions that control, and cure of cancer by establishing units within NCI Cancer Centers – including Centers with 

increase the pace of and without the “comprehensive” designation – to work with the Centers for Disease Control and 

translational research Prevention and state and local governments. $16.00 M 

and the rate at which ■ Continue to develop a biomedical informatics system common to all Cancer Centers to increase 

the results of research collaborations between Centers and further the sharing of research results. (See page 97.) 

are translated into 

■ Pilot new outreach and education strategies at Cancer Centers to reach the broadest possible clinical practice and population. $3.00 M 

public health benefit. 

2. Increase the effectiveness of collaborations to improve access of minority 

populations to state-of-the-art clinical and population studies, cancer treatments, technologies, and care. $10.00 M 

■ Enhance the research capabilities of minority and minority-serving institutions (MSIs) and improve 

the effectiveness of Cancer Centers in serving minority communities by strengthening formal partnerships between Cancer Centers and MSIs. $8.00 M 

■ Integrate NCI-designated Cancer Centers and Minority Institution/Cancer Center Partnerships with 

the NCI Special Populations Networks for Cancer Awareness Research and Training. $2.00 M 

The Cancer Genetics Network is a nationwide system of research sites located within NCI-designated Cancer Centers. The CGN specializes in the study of inherited 

predispositions to cancer. This ambitious program now has its essential databases 

in place and has achieved adequate participation from patients. Poised as a major 

research arm in genetics, the CGN has begun collaborating on several projects with 

the SPOREs and with individual investigators. (See page 11.) 

The Mouse Models of Human Cancers Consortium is a powerful system for engaging researchers in a wide spectrum of basic, translational, clinical, and epidemiological investigations. (See page 18.) For the first time, a resource is available to the 

scientific community that documents the characteristics of mouse models and supplies the most valuable cancer models to the scientific community. The Consortium 

investigators are collaborating with independent investigators supported by traditional research grants and with SPORE and Early Detection Research Network 

82 The Nation’s Investment in Cancer Research 
3.	 Expand the capacity of NCI Cancer Centers, Centers of Excellence, networks, 

and consortia to engage in newly developing areas of research and technology 

and to act as platforms for translating discoveries into interventions. $58.50 M 

■ Build the clinical and population research infrastructures of NCI-designated Cancer Centers. Fund 

databases that conform to NCI’s clinical informatics infrastructure; support the development and 

expansion of population databases and other resources; provide more core staff to conduct innovative translational therapeutic and prevention trials; and strengthen the auditing and data safety and 

monitoring of human subjects research. $25.00 M 

■ Expand the conduct and impact of translational research by promoting and developing partnerships 

among NCI-designated Cancer Centers and industry; national, private, state, and community 

organizations; and other cancer funding organizations. $2.50 M 

■ Maximize collaborative research opportunities and facilitate integration of best practices, sharing of 

protocols, and consolidation of functions to avoid duplication of resources, by providing leadership 

and coordination to NCI-designated Cancer Centers, Centers of Excellence, networks, and consortia. $0.50 M 

■ Expand and refine the tissue banks and tissue procurement systems of Cancer Centers in order to 

meet a national standard and increase the potential for collaborations in translational research. 

$17.50 M 

■ Strategically expand SPOREs by adding two to three SPOREs to cancer disease sites that lack a 

critical mass to function maximally in translational research. $8.00 M 

■ Stimulate inter-SPORE research, early phase clinical trials, and collaborations with other NCI networks, Centers of Excellence, and consortia by expanding the supplement programs for SPOREs. 

$5.00 M 

Management and Support $ 0.80 M 

Total $96.80 M 

investigators. (See page 18.) Interactions among the Early Detection Research 

Network, SPOREs, and other interdisciplinary groups are facilitating the discovery 

and development of molecular markers and assays that detect early signs of cancer. 

Through its Minority Institution/Cancer Center Partnership Program (MICCP), 

NCI is helping to increase the competitive research grants obtained by minority 

institutions. All major U.S. minority institutions with medical schools now participate in the program. Over 30 other institutions that have never been involved in 

cancer research are also participating. New inter-institutional models are emerging 

that provide direction for minorities as they develop their skills in cancer research. 

(See page 61.) In another NCI effort, Special Populations Networks for Cancer 

Awareness and Training are building relationships between minority communities, 

NCI-designated Cancer Centers, and NCI Cooperative Groups to address cancer 

health disparities in specific populations. (See page 58.) 

A Plan and Budget Proposal for Fiscal Year 2005 

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

83 
NCI Partners To Advance Cancer Research 

NCI is increasingly looking beyond its institutional boundaries to engage in diverse partnerships with public, 

private, and academic sectors. 

NCI’s partnership goals aim to:


• Eliminate bottlenecks and foster an “enabling culture” to 

accelerate progress against cancer. 

•	 Leverage funding to take advantage of expertise outside of the 

Institute. 

•	 Build synergy and create a feeling within the cancer community 

that we are all in this fight together. 

A few of these partnerships are described here to illustrate the depth and 

breadth of our partnership portfolio. 

Medical researchers Among intra- and extramural investigators . . . 

examine a sequence At the heart of the Leukemia/Lymphoma Molecular Profiling Project (LLMPP) is a 

gel x-ray to determine consortium of NCI intramural and extramural investigators who have pooled 

the pattern of DNA. resources and talent to define the molecular classification of lymphomas. In one 

project, the group used the tissue collections of member institutions to define subtypes of diffuse large B-cell lymphoma that are associated with differing clinical 

responses to treatment. The large number of samples, substantially more than any 

single institution could have acquired, have allowed the researchers to draw reliable 

conclusions about how best to diagnose and treat patients based on the molecular 

subtype of their disease. 

With other Federal agencies . . . 

Through an interagency agreement, NCI and the Food and Drug Administration 

(FDA) recently collaborated to share knowledge and resources to facilitate the development of new cancer drugs and speed their delivery to patients. A task force, with 

chairs from both NCI and FDA and other senior staff from both agencies, will oversee implementation of this agreement. (See page 88.) 

With pharmaceutical companies . . . 

In 1999, NCI and the pharmaceutical company Genentech entered into a cooperative 

research and development agreement (CRADA). Under this CRADA, NCI and 

Genentech conducted a clinical trial to test treatment of renal cell carcinoma (RCC) 

patients with the monoclonal antibody AvastinTM (bevacizumab). Avastin targets a protein involved in the angiogenesis (development and maintenance of new blood vessels) 

that is required for renal cell tumor growth. Cancer progression was slower in patients 

treated with Avastin in addition to standard interferon therapy than in patients given 

interferon and a placebo. These preliminary findings provide the basis for a larger trial 

to determine whether Avastin treatment can improve survival in RCC patients. Avastin 

also looks promising for treatment of breast and colorectal cancers. (See page 87.) 

84	 The Nation’s Investment in Cancer Research 
Other partnerships 

highlighted in 

this document 

• 

page 13 

• 

Sequencing, page 17 

• Quality Enhancement 

• 

• 

Cancer SPOREs, page 80 

• Advanced Magnetics Inc., 

and Combidex®, page 36 

• Novartis and GleevecTM, 

page 87 

• Searle and Celecoxib, 

page 87 

• Asian American/Pacific 

Islander mammography 

page 101 

• 

National Surgical Adjuvant 

Breast and Bowel Project, 

Massively Parallel Signature 

Research Initiative, page 54 

Transdisciplinary Tobacco 

Research Centers, page 39 

Avon Foundation and Breast 

education resource, 

Research Tested Intervention 

Programs, page 101 

A partnership with Millenium Pharmaceuticals yielded VelcadeTM, a drug that 

inhibits a class of proteins known as proteasomes, which are implicated in cancer 

development. The NCI/Millenium partnership is allowing Velcade to rapidly move 

through the drug development pipeline, expediting its availability to patients. In 

2003, FDA approved Velcade for treatment of multiple myeloma patients who have 

received at least two prior therapies. NCI-sponsored clinical investigators are now 

evaluating Velcade therapy for newly diagnosed multiple myeloma patients. For more 

information, see page 89. 

With bioinformatics companies . . . 

NCI, FDA, and Correlogic Systems Inc., a bioinformatics company, are engaged in 

scientific collaboration in clinical proteomics (the study of protein structure and 

function). The partners are developing an approach for early detection of ovarian 

and prostate cancers based on protein profiling, a complex analysis of proteins present in individual blood samples. A clinical trial using protein profiling to monitor 

ovarian cancer recurrence is underway. This technology also shows promise for 

diagnosing cancer, monitoring toxicity, determining the efficacy of therapy, and 

conducting follow-up surveillance. 

Beyond traditional partnerships . . . 

NCI, with Cancer Care, the Intercultural Cancer Council, Living Beyond Breast 

Cancer, and the Lance Armstrong Foundation partnered to produce the teleconference series “Cancer Survivorship: Living with, through, and beyond Cancer.” Over 

1,000 people participated in each of three sessions in spring 2003. The interest in 

this series underscores the importance of collaborations for the diffusion and dissemination of evidence-based information to the public. 

A new initiative, called the Academic Public Private Partnership Program (AP4), is 

supporting the discovery of new cancer agents and their rapid translation to human 

clinical trials. Through this program, NCI fosters collaborations among universities, pharmaceutical companies, biotech companies, and nonprofit organizations. 

A new funding mechanism to support such broad-based collaboration was called for 

by several NCI Progress Review Groups. (See page 6.) The AP4 initiative represents 

a new paradigm in drug discovery, development, and delivery for NCI. 

NCI has partnered with the Centers for Disease Control and Prevention, the 

Substance Abuse and Mental Health Services Administration, and the American 

Cancer Society to provide evidence-based tools to help communities better understand and address their cancer burden. The Web-based tools are available through 

a Web portal called Cancer Control PLANET (Plan Link Act Network) located at 

cancercontrolplanet.cancer.gov. The Agency for Healthcare Research and Quality

will be adding links to more cancer prevention Web sites. States and communities 

can use these tools to plan, implement, and evaluate evidence-based comprehensive 

cancer control programs. 

A Plan and Budget Proposal for Fiscal Year 2005 85 

P L A T F O R M S F O R D I S C O V E R Y, D E V E L O P M E N T , A N D D E L I V E R Y 
NCI-supported clinical trials provide a crucial infrastructure for moving new cancer interventions from the 

laboratory to studies in people with, or at risk for, cancer and then to the health care setting. These clinical 

trials have always included investigations of a broad set of interventions — chemoprevention, chemotherapy,

radiation, and surgery — sometimes used alone and sometimes in combination. With recent advances in 

deciphering the molecular changes that cause cancer, a new paradigm of cancer treatment and prevention

research is emerging and bringing with it the promise of an exponential growth in effective cancer interventions. Increasingly, new anti-cancer agents are directed at distinct molecular targets within cancer cells, 

leaving healthy cells unharmed.

NCI currently provides leadership, resources, and expertise at all stages of clinical

development for molecularly targeted agents. In the early stages of research, when

candidate drugs are first identified and shown to have promise, NCI forms collaborations and partnerships that help researchers from public, industrial, and 

academic settings develop anti-cancer agents for a broader array of tumor types and

at a faster pace than would otherwise be possible. Partners work together to establish “proof-of-principle” in early clinical trials. Then they move rapidly to verify the

presence of relevant molecular targets in populations of patients and persons at risk

for cancer and to test for improvements in outcomes such as prevention, tumor

response, and improved quality of life and survival. For Phase III trials, NCI 

provides resources to test promising leads in large numbers of patients. 

While much has been accomplished to streamline cancer clinical trials, NCI must

further accelerate movement of promising research discoveries into clinical development and delivery to the public. We must:

• Identify the most important questions in prevention and treatment that can be

addressed through clinical trials. 

• Create flexible mechanisms that allow for easy collaboration among basic 

scientists, clinicians, industry, academia, and NCI.

• Explore the use of combinations of molecularly targeted agents for treating cancer by targeting several critical points in cancer causing molecular pathways.

(See page 92.) 

• Develop surrogate endpoints to identify the most promising treatment or 

prevention agents for movement into large, easily accessible trials.

• Improve support to physician researchers.

• Improve access to clinical trials by physicians, patients, and those at risk of cancer.

• Help ensure that treatments are made available to all patients who need them,

including minority and underserved populations.

86 The Nation’s Investment in Cancer Research

National Clinical Trials Program in Treatment and Prevention
PROGRESS IN PURSUIT OF OUR GOAL 

Building Public-Private Partnerships for Clinical Trials Research 

NCI is expanding its role in public-private partnerships as more private-sector companies begin to develop anti-cancer drugs. Because pharmaceutical companies tend 

to seek FDA approval or licensing of a new agent for one or a few tumor types, NCI 

can help ensure that new agents are evaluated against a fuller range of cancers (or 

precancers) and in combination with treatments such as surgery, radiation therapy, 

or other drugs. In one recent success, the collaboration between Novartis and NCIsupported researchers led to the development of GleevecTM (imatinib mesylate) to 

treat chronic myelogenous leukemia and now gastrointestinal stromal tumors, in 

both adult and pediatric patients. In an ongoing partnership with Genentech, NCIsupported clinical investigators are testing a promising molecularly targeted drug, 

AvastinTM (bevacizumab), in patients with advanced colorectal cancer who were 

previously treated by chemotherapy.1 In a partnership with Searle and Pfizer Inc., 

researchers found that the arthritis drug, celecoxib, can reduce the number of 

precancerous colon polyps in patients with familial adenomatous polyposis, an 

inherited syndrome that predisposes them to colon cancer. Researcers are also testing celecoxib for prevention and/or treatment of head and neck and other cancers. 

Building Collaborations among Laboratory and Clinical Scientists 

NCI also recognizes the increasing need for collaboration with laboratory scientists 

in conducting clinical trials for molecularly targeted agents. The cellular pathways 

and interactions involved in these molecular targets are extraordinarily complex 

and interrelated, and they require scientists to develop new techniques and tests to 

identify patients whose tumors contain the relevant targets and to monitor drug 

effects during treatment. More than half of NCI-sponsored cancer treatment trials 

initiated over the last 2 years have included correlative studies with laboratory 

scientists, and this trend is increasingly seen in cancer prevention trials. 

Simplifying Administration of Clinical Trials 

NCI continues to simplify the administration of NCI-supported clinical trials to 

make it easier for physicians and their patients to participate. In 2000, we launched 

the online Cancer Trials Support Unit (CTSU) Website to centralize the common 

administrative, financial, and data collection activities of NCI’s clinical trials cooperative groups. Since May 2002, physicians outside NCI cooperative groups have 

also been able to enroll patients into these NCI-sponsored clinical trials. 

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

1 Irinotecan, 5-fluorouracil (5-FU), and leucovorin 

A Plan and Budget Proposal for Fiscal Year 2005 87 
their delivery to patients. 

• 

• 

• 

• 

development of clinically meaningful endpoints. 

• 

• 

• 

NCI and FDA Partner 

Drug Development 

“The collaboration will help our two agencies take full advantage of our combined 

knowledge base at a time when many 

— 

“FDA is committed to finding better ways to 

possible. At a time when the opportunities 

our colleagues at the National Cancer 

Institute will help us fulfill that mission.” 

— Mark B. McClellan, M.D. 

In May 2003, NCI and the Food and Drug Administration (FDA) announced a joint effort to streamline cancer drug development. Under a multi-part Interagency Agreement, the two agencies will share knowledge and resources to enhance 

the efficiency of clinical research and the scientific evaluation of new cancer medications. Federal researchers and regulators will be working more effectively than ever before to facilitate the development of new cancer drugs and speed 

This new partnership will broaden existing and create new joint programs to: 

Develop biomarkers for use as surrogate markers in clinical trials. 

Create a cancer bioinformatics infrastructure to improve data collection, integration, and analysis for 

preclinical, pre-approval, and post-approval research. 

Address joint technology development issues in proteomics and other areas. 

Advance the process for developing and evaluating cancer chemoprevention agents, including the 

Improve consumer awareness of the consequences of their choices about diet and nutrition for cancer 

prevention. 

Enhance staff capabilities through collaborative training, joint rotations, and joint appointments. 

Conduct a systematic review of current policies to identify other ways in which NCI-FDA collaborations can 

enhance the development and regulatory process for cancer technologies. 

to Streamline Cancer 

new kinds of anti-cancer agents are in the 

pipeline. Molecularly targeted drugs and 

other novel agents offer great promise, 

but they also present new challenges that 

require more collaboration.” 

Andrew C. Von Eschenbach, M.D. 

Director, NCI 

get safe and effective treatments to patients 

with life-threatening diseases as quickly as 

to reduce the burden of cancer are greater 

than ever, sharing tools and resources with 

Commissioner, FDA 

Making Strides in Cancer Treatment through Clinical Trials 

NCI’s focused investment in treatment trials is paying off with increased survival 

and better quality of life for patients with a variety of cancers. Just a few of the 

advances emerging from recent clinical trials are listed here: 

•	 In breast cancer patients who have experienced metastasis to at least one 

lymph node, adding the drug paclitaxel to standard adjuvant chemotherapy of 

adriamycin and cytoxan (AC) improved disease-free survival by 17 percent. 

Furthermore, patients treated with a dose-dense chemotherapy regimen, where 

treatments are given over shorter intervals, received the most benefit from paxlitaxel (82 percent versus 75 percent disease-free survival compared to standard 

administration). As a result of this discovery, 4,000 more women could be alive 

and disease-free 4 years after diagnosis. 

88 The Nation’s Investment in Cancer Research 
Velcade is the first in a 

new class of molecularly 

targeted anti-cancer 

agents known as proteasome inhibitors. See 

“Story of Discovery: 

Harnessing Apoptosis to 

Destroy Cancer Cells” in 

The Nation’s Investment 

in Cancer Research: 

A Plan and Budget 

Proposal for Fiscal Year 

2004 (plan2004.cancer.gov).

From years of scientific 

research, we know that 

cancers are not caused 

by a single, catastrophic 

event, but result from 

a complex and longevolving process. 

•	 A Phase III clinical trial demonstrated that adjuvant chemotherapy can improve 

survival in women with endometrial cancer. Following hysterectomy, staging, 

and tumor debulking, women with advanced endometrial cancer who received 

systemic chemotherapy with the drugs cisplatin and doxorubicin survived, on 

average, 33 percent longer than those treated with standard radiation treatment. Approximately 4,000 to 5,000 women per year may benefit from this 

new treatment approach. 

•	 In partnership with Millennium Pharmaceuticals, Inc., NCI has been studying 

the use of VelcadeTM (bortezomib) in patients with refractory or relapsed myeloma. In a recently completed Phase II clinical trial, 30 percent of patients 

responded well to Velcade over the course of about a year. Investigators are now 

conducting follow-up studies and have begun evaluating Velcade in newly 

diagnosed multiple myeloma patients. Other investigators are discovering antitumor effects of Velcade in breast, non-small cell lung, neuroendocrine, and 

renal cancers, as well as in melanoma, sarcoma, chronic myelogenoius 

leukemia, and non-Hodgkin’s lymphoma. 

Making Strides in Cancer Prevention through Clinical Trials 

Since many cancers take decades to develop, we have the time and opportunity to 

intervene to stop or reverse their progress. NCI’s prevention trials seek to determine 

which person is at risk for cancer, define ways to prevent or reduce that risk, detect 

cancer at its earliest stages, and actively intervene to prevent invasive cancer. The 

following represent a small sampling of the progress in these areas: 

•	 In June 2003, researchers of the Prostate Cancer Prevention Trial presented the 

first-ever findings that prostate cancer can be prevented, at least in part, by drug 

intervention. Men in the study who took the drug finasteride for 7 years were 

25 percent less likely to develop prostate cancer than men taking a placebo. 

However, those trial participants who did develop prostate cancer while taking 

finasteride experienced a slightly higher incidence of potentially aggressive 

tumors. Further study of finasteride therapy is needed. 

•	 Daily aspirin may be an appropriate supplement to regular surveillance procedures for many men and women at increased risk for colorectal cancer. 

Through two large randomized trials, investigators confirmed earlier observational studies that daily aspirin can reduce the development of colorectal 

polyps. On average, patients at increased risk for colorectal cancer who took 

daily aspirin for as few as 3 years reduced their colorectal polyp development 

by 35 percent. People considering aspirin therapy should consult their physician 

to discuss risks and benefits. 

•	 Data from the landmark Breast Cancer Prevention Trial show that women 

at high risk for breast cancer who received tamoxifen, especially women under 

age 50, developed fewer cases of benign breast disease and, consequently, were 

better able to avoid invasive follow-up biopsies. 

P L

ATFORMS FOR DISCOVE

R

Y, DEVELOPMEN

T, AND DELIVE

R Y 

A Plan and Budget Proposal for Fiscal Year 2005 89 
NATIONAL CLINICAL TRIALS PROGRAM IN TREATMENT AND PREVENTION 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Ensure that NCI’s 1. Identify and accelerate development of the most promising new agents for 

Clinical Trials Program cancer treatment and prevention. $84.70 M 

is poised to address ■ Expand partnerships and create flexible collaborations with industry, the FDA, and other public, prithe most important vate, and academic organizations to bring together the best laboratories, institutions, and investimedical and scientific gators (including surgeons, pathologists, and radiologists, in addition to traditional participants) for 

questions in cancer early translational research. $4.00 M 

prevention, treatment, ■ Expand resources for the Rapid Access to Intervention Development (RAID) and Rapid Access to 

and quality of life Prevention Intervention Development (RAPID) programs. (See pages 28-29, Objectives 2 and 3.) 

quickly and effectively 

through state-of-the-

■ Facilitate early proof-of-principle clinical trials by expanding capacity to file Investigational New Drug 

Applications and New Investigational Technology Applications. $0.70 M 

art clinical trials. ■ Create broadly-based working groups to identify clinically relevant surrogate endpoints and develop 

standardized resources to validate these endpoints. $2.00 M 

■ Expand translational research capacity to use correlative studies more extensively. $8.00 M 

■ Develop resources to assess the effects of promising agents on their molecular targets through 

increased funding of Interdisciplinary Research Teams for Molecular Target Assessment. 

$20.00 M 

■ Develop molecular assays required to characterize/classify tumors, and make them widely available. 

Support a national tissue resource to facilitate rapid evaluation of new assays and relevant clinical 

correlations as new targets are identified. (See page 28, Objective 2.) 

■ Increase the pace of development and clinical testing of promising new therapeutic and preventive 

agents by: 1) increasing the number of promising agents entering clinical trials, 2) increasing the 

number of, and tripling patient accrual, to pivotal early clinical trials, 3) providing financial incentives 

for timely initiation and conduct of clinical trials, and 4) expanding the rapid grant review process, 

Quick Trials, for mechanism-based clinical trials. $35.00 M 

■ Support the NCI intramural clinical trials program by increasing the number of data managers, 

research nurses, biostatisticians, and clinicians available to support a critical mass of clinical investigators, and continuing the Tissue Array Research Program to identify key molecular alterations in 

cancers. $15.00 M 

2. Strengthen scientific planning and leadership for the large, definitive clinical 

trials that evaluate and define the efficacy and clinical benefit of new treatments and prevention strategies. $25.00 M 

■ Identify and address compelling clinical questions confronting physicians and their patients under 

treatment for cancer or at high risk of cancer. $17.00 M 

■ Expand state-of-the-science meetings to identify important research questions and develop scientific strategic plans to address them in disease settings not currently covered, including pediatric 

tumors. Continue to include broad representation from the scientific community, both basic and 

clinical, as well as the advocacy community. $1.00 M 

■ Expand clinical trials planning to address critical questions across the major types of conditions 

experienced by patients by: 1) integrating cross-disciplinary and patient advocate input into scientific strategic planning, 2) supporting multidisciplinary scientific leadership of clinical trials, and 

3) integrating biomarker, behavioral, epidemiologic, outcome and other research into existing 

clinical trials. $1.00 M 

90 The Nation’s Investment in Cancer Research 
■ Provide additional research funds for leadership support of scientists who are responsible for writing, monitoring, and analyzing NCI-sponsored, high-priority Phase III trials, including researchers 

who chair studies in addition to caring for patients, and study statisticians. $5.00 M 

■ Enable correlative studies and long-term follow-up for future evaluation of new assays and biomarkers by increasing funding for tissue banks. $1.00 M 

3. Double the rate at which Phase III trials are completed. $223.50 M 

■ Increase the number of patients accrued to national trials and shorten the duration of accrual by: 

1) increasing funding for nursing, data management, and other infrastructure costs at local clinical 

trial sites and for operations, data management, and statistical offices, and 2) increasing the number and capacity of existing Community Clinical Oncology Programs. 

■ Facilitate greater investigator participation in clinical trials by: 1) initiating a “start-up” loan program 

for new investigators to fund training, research nurse support, and data management, 2) reducing 

administrative burdens of clinical trials participation, and 3) shortening development and activation 

of new clinical trials through broader implementation of the Central Institutional Review Board, more 

rapid protocol development and review, and other mechanisms. 

■ Provide extensive information about treatment and prevention clinical trials to enable patients and 

physicians to make informed choices by: 1) incorporating NCI educational materials into marketing 

and communications strategies (working with the NCI Offices of Communications and Education, 

patient advocacy groups, professional societies, and others), and 2) developing novel strategies, 

including the use of alternative media, for working with minority and underrepresented patient 

populations and their primary care physicians. 

■ Consolidate administrative tasks and improve quality assurance functions by 1) providing a single 

interface for investigators to enroll patients, 2) expanding the Cancer Trials Support Unit, 3) developing uniform electronic case report forms and data reporting systems, and 4) expanding NCI’s 

audit program. 

■ Facilitate efficient collection, analysis, and sharing of clinical trials data for current and future use in 

association with tissue specimens in tissue repositories and banks, by maintaining state-of-the-art 

informatics systems. 

4. Ensure that clinical trials are broadly accessible to cancer patients, populations at risk for cancer, and the physicians who care for these groups. 

■ Increase access for minority and underserved populations to state-of-the-art clinical trials. (See 

pages 62 and 63, Objective 3.) 

■ Provide funding directly to patients with special needs to cover costs associated with travel, childcare, and other relevant expenses that might limit participation. Address barriers to access for 

patients dependent on state and Federal health agencies for healthcare coverage by working with 

state and local government agencies, the Indian Health Service, and other gatekeepers. 

■ Encourage local sites to identify existing resources to help minority and underserved patients receive 

appropriate follow-up care and ensure that follow-up care is offered. 

Management and Support $ 1.70 M 

Total $334.90 M 

A Plan and Budget Proposal for Fiscal Year 2005 

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

91 
p70s6k 4E-BP1 

is used to slow the 

The mutated Ras 

pathway is targeted 

by a farnesyl 

transferase 

inhibitor drug. inactive allows for the progression 

of malignancy along another 

is used to halt cancer 

progression along 

Raf 

MEK 

MAPK 

P13K 

Akt 

the Ras protein, 

promoting the 

progression of cancer 

along one branch 

A mutation leads to amplification 

of the receptor tyrosine kinase (RTK) 

growth factor pathway. 

An RTK inhibitor drug 

accelerated pathway. 

A mutation that renders PTEN 

branch of the pathway. 

An mTOR inhibitor 

this pathway. 

mTOR 

T H R E E D R U G S C O M B I N E T O A R R E S T M A L I G N A N C Y 

A mutation activates 

of the pathway. 

Targeting Signaling Cancer is caused by mutations in genes that in turn alter the structure of proteins that regulate 

Pathways with Drug molecular pathways for cell growth and other important functions. To improve patient outcomes, 

Combinations researchers hope to develop and test in the clinic, therapies that use combinations of drugs to 

target several critical points in cancer-causing molecular pathways. This diagram shows how three 

drugs might be used in combination to shut down a pathway with multiple proteomic changes. 

92 The Nation’s Investment in Cancer Research 
Application 

NCI Intramural Research Program Provides a 

Platform for Innovation, Translation, and 

NCI’s Intramural Research Program (IRP), which conducts research at NIH research 

laboratories and clinics, provides a unique venue for innovation, translation, and 

application, and complements our robust Extramural Research Program. The intramural environment promotes and encourages innovation and serves as a proving 

ground for longer-term, high-risk/high-impact projects. This is possible because the 

IRP can make long-term funding commitments and support. The Program provides 

exceptional translational research opportunities that exploit the close linkages 

among investigators conducting basic, clinical, and population research. It allows 

immediate application of technological advances to biomedical research and 

enables rapid response to urgent public health needs. Clinical researchers have 

access to the facilities of the NIH Clinical Center, and with them, the quality medical 

care that is provided without charge to patients enrolled in NCI clinical trial protocols. 

The intramural environment promotes and encourages 

innovation and serves as a proving ground for longer-term, 

high-risk/high-impact projects. 

IRP plans include objectives to: 

•	 Enhance the unique value of the Program by facilitating more interactions and 

collaborations among intramural investigators. 

•	 Increase interactions and collaborations with extramural investigators, and 

expand interactions with the public and private sectors. 

•	 Develop innovative new technologies and approaches for cancer discovery, 

prevention, detection, diagnosis, and treatment. 

•	 Facilitate the development of a unique clinical research program for delivery of 

novel interventions for prevention and therapy. 

•	 Foster training to ensure excellence and to address the need for new, interdisciplinary approaches to cancer research. 

•	 Implement a review and reward structure that will encourage innovation and 

collaboration while maintaining scientific excellence. 

The opening of the new NIH Clinical Center facility in 2004, the establishment of 

new consortia linking extramural and intramural investigators, the development of 

new technologies, and new efforts to foster interdisciplinary approaches to scientific discovery will strengthen the work of NCI’s Intramural Research Program. 

Its unique contributions will help us meet our Challenge Goal to eliminate the 

suffering and death due to cancer. 

P L AT F O R M S F O R D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

A Plan and Budget Proposal for Fiscal Year 2005 93 
Dissemination 

Enablers of Discovery, Development, and Delivery: 

Strengthening Tools for Analysis, Resource Sharing, and 

Case control and cohort studies rely on high throughput genotyping, studies in integrative cancer biology 

require computational models, large clinical trials require the recording and tracking of enormous amounts of 

information, and protein pattern analysis puts to use the latest developments in artificial intelligence. 

It is vital that investigators carrying out state-of-the-art studies have access to the 

Bioinformatics tools that will support these and other needs for data analysis and 

resource sharing. The cancer research community must act now to harness contemporary bioinformatics tools for integrating diverse data types, conducting 

analyses with accuracy and speed, capturing and sharing research outcome data, 

and providing user-friendly tools that permit patients and their advocates to interact more directly with the cancer research community. NCI will accomplish this 

by using requested funding to establish a network of information technology 

partners and support development of a shared bioinformatics infrastructure and 

tools that facilitate data mining and integration. 

The explosive rise of the Internet continues to fuel the demand for accessible health 

information, but substantial research reveals gaps between the information people 

want and what they receive. Moreover, people with less income and education are 

disadvantaged with respect to health communication. This is especially evident with 

patient-provider communication. NCI leads our Nation’s Cancer Communications 

research and development efforts and plays a central role in delivering vast amounts 

of information to diverse audiences every day. The research focuses on how people 

inform, persuade, relate to, and influence each other in various contexts and cultures. Larger investments in cancer communications will enable the translation of 

successful intervention research into practice. In particular, we must apply what we 

have learned through research to strengthening communications with and improving the health of underserved populations. And optimizing communications to 

speed the process from discovery to the dissemination of evidence-based interventions is at the forefront of our responsibilities. We must ensure that every person 

gets needed information at the appropriate time and in a form that is comprehensible 

and useful as well as culturally and linguistically appropriate. 

94 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 95

E N A B L E R S O F D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY

Bioinformatics

The exponential expansion of biomedical knowledge is generating a tidal wave of data. As biomedical

research becomes an increasingly collaborative undertaking, the research arena is finding itself hampered by the “silo” approach to solving data management challenges. Most existing databases have

developed independently, with tremendous variability in rules, processes, vocabularies, data content,

and analytical tools. There is no unifying architecture to support the essential interoperability among

databases and exchange of data. Parallel advances in bioinformatics are needed to address these

issues and to accelerate the pace of discovery within and across scientific research centers.

NCI’s bioinformatics strategy is to use information technology to integrate biomedical

information in order to make it accessible to researchers across disciplines. Such harmonization will have a major national impact. For example, collaborations among

individuals and institutions will become easier to initiate and carry out, clinical trials

will be completed more quickly in multi-institutional settings, and the critical new

frontier of genotype-phenotype correlative analyses will be greatly facilitated. 

Our long-term goal for bioinformatics is to redefine how research is conducted, care

is provided, and patients and participants interact with the biomedical research

enterprise. We will do this by building an interconnected web of data, individuals,

and organizations and making it accessible to all who need it. 

To achieve this goal, NCI will:

• Create and implement an informatics platform that integrates diverse data types

and analytic tools and facilitates the sharing of data among investigators within and

across disciplines.

• Capture and share data from clinical studies by linking networks of community practitioners, clinical research organizations, managed care providers, advocates,

academic centers, and individuals.

• Create a consortium for developing a novel infrastructure and tools to facilitate

complex biomedical data mining and integration.

Bioinformatics technology ensures that the growing tide of cancer information is

made available to individuals, groups, and institutions for research and clinical

practice. The goal of NCI’s Center for Bioinformatics (NCICB) is to maximize interoperability and integration of research-related information resources to support

NCI research initiatives. This support includes bioinformatics platforms, services,

tools, and data. The Center participates in the evaluation and prioritization of

NCI's bioinformatics research portfolio, conducts and facilitates bioinformatics

research, and serves as the locus for strategic planning to address expanding

informatics needs. The Center establishes information technology and exchange

standards both within and outside of NCI.

NCI’s Center for

Bioinformatics Serves 

as an Integrator for

Cancer Research 
PROGRESS IN PURSUIT OF OUR GOAL 

Support to Developing New Bioinformatics Tools and Infrastructure 

Discovery, Unprecedented amounts of data and information — clinical trial results, molecular 

Development, signature information, and preclinical and animal models — are available to 

and Delivery current researchers. However, many of the systems in which this rich and sophisticated collection of data is stored are incapable of communicating with other systems. 

NCI is committed to developing a means to address this complexity by integrating 

and synthesizing data. NCI is currently developing a spectrum of infrastructure, 

tools, templates, and standards for biomedical informatics that can meet the needs 

of the cancer research community. We collaborate with a variety of institutions and 

make our products and services available at no cost to scientists. 

Biomedical informatics systems are integral to NCI’s Cancer Therapeutics 

Evaluation Program, the NCI Center for Cancer Research, the Cancer Biomedical 

Imaging Program, the Specialized Programs of Research Excellence, the Director’s 

Challenge microarray initiative, the Cancer Genome Anatomy Project, and the 

Mouse Models of Human Cancers Consortium, as well as numerous cancer prevention trials. Through the Cancer Molecular Analysis Project (CMAP), NCI facilitates the identification and evaluation of molecular targets by integrating comprehensive molecular characterizations of cancer and making the data and infrastructure publicly accessible. CMAP permits investigators to discover molecular targets, 

assess their validity and interaction with other targets, determine if there are therapeutic agents that can act on specific targets, screen for possible toxicity, and determine whether there are clinical trials evaluating these agents. 

Setting Standards That Allow Systems to “Talk” with One Another 

NCI’s Center for Bioinformatics has developed the cancer Common Ontologic 

Reference Environment (caCORE), a system for combining and generating knowledge. A key component of the caCORE is NCI’s Enterprise Vocabulary Services 

(EVS). Collaboratively developed, the EVS team organizes and translates the distinct and overlapping vocabularies of scientific projects via one common vocabulary and two broadly used vocabulary resources, the NCI Thesaurus and 

Metathesaurus. The EVS team also works with vendors to create and improve tools 

for vocabulary development and curation. 

Partnering to Leverage Resources and Encourage Growth 

New strategic partnerships are underway to promote the integration of 

disparate bioinformatics efforts throughout the cancer research community, establish common language, and promote sharing of bioinformatics infrastructure and 

data. One such partnership is between NCI and the NCI-supported Cancer Centers. 

The focus of this partnership is on building a coordinated program to leverage existing 

infrastructure and inform future development across NCI and the entire community 

of Cancer Centers. In its pilot phase, the program will fund a small number of 

representative Cancer Centers that will be responsible for broadly assessing requirements, 

96 The Nation’s Investment in Cancer Research 
BIOINFORMATICS 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Support to Discovery and Development Redefine how 

1. 	 Enable data generated among investigators in diverse disciplines to be trans- research is conducted, parently connected and shared by creating and implementing an informatics care is provided, platform that integrates diverse data types and analytic tools. $20.00 M 

and patients and 

participants interact ■ Complete the pilot of an NCI-developed informatics platform in a selected group of Cancer Centers, 

Specialized Programs of Research Excellence (SPOREs), and NCI intramural laboratories. $5.00 M with the biomedical 

research enterprise ■ Refine current and develop additional modules, software bridges, and infrastructure extension 

by building the based on the results of the pilot. $2.50 M 

necessary intercon- ■ Expand NCI help desk capabilities to better serve the needs of the project. $2.50 M 

nected web of data, ■ Make the resources available to additional Cancer Centers, SPOREs, and intramural groups. 

individuals, and $10.00 M 

organizations and 

making it accessible 

to all who need it. 2. Facilitate complex biomedical data mining and integration by creating a 

consortium charged with developing a novel infrastructure and tools. $10.00 M 

■ Identify academic, government, and industrial developers who are willing to produce open-source 

tools that are interoperable with NCI’s architecture and support community identified needs and 

NCI-determined priorities. 

■ Establish a mechanism for working together to develop data mining and data integration tools. 

Support to Delivery 

3. 	 Link networks of community practitioners, clinical research organizations, 

managed care providers, and academic centers by capturing and sharing 

data from clinical research investigations. $10.00 M 

■ Capture clinical research data through a Web-based reporting system piloted with volunteers from 

SPOREs, Cancer Centers, and NCI intramural groups. $5.00 M 

■ Extend the infrastructure to permit integration with and sharing of other data types and to support 

clinical research beyond therapeutic and prevention trials. $1.00 M 

■ Pilot in additional cancer research settings a Web-based clinical trials support infrastructure developed in the NCI Intramural Program, SPOREs, and Cancer Centers. $2.00 M 

■ Develop open source clinical trials modules that can be freely distributed to other academic 

research centers, community practices, and private practices. $2.00 M 

Management and Support 	 $ 0.80 M 

Total $40.80 M 

E N A B L E R S O F D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

A Plan and Budget Proposal for Fiscal Year 2005 97 
common web of communications, data, and applications. 

The caBIG pilot includes: 

• 

• 

implement or adapt them for local needs 

• 

caBIG.nci.nih.gov) and 

• 

• 

• 

caBIG Will 

Expedite Access 

to Bioinformatics 

NCI plans to deploy a biomedical informatics infrastructure called the cancer 

Biomedical Informatics Grid or caBIG. As part of this effort, NCI, in partnership with others in the cancer research community, is creating a common, extensible informatics 

platform that integrates diverse data types and supports interoperable analytic tools. 

This platform will allow research groups to tap into the rich collection of emerging 

cancer research data while supporting their individual investigations. 

Because Cancer Centers provide the institutional framework around which much of 

NCI-supported research is conducted, NCI is working with a representative sample of 

these Centers in the pilot phase of the project. Center resources will be joined into a 

“Co-developers” that contribute mature infrastructure and applications 

“Adapters/adopters” that take contributed infrastructure and applications and 

“Users” that utilize the applications and infrastructure provided, contribute data sets 

and study populations, and assist in establishing the needed functionality of the caBIG effort 

NCI is soliciting ongoing feedback from the Cancer Centers through working groups engaged in specific development areas, workshops to review models and system development, and a project Website (

mailing list. The workshops and Website are available to the entire cancer research community. As consensus is 

achieved, projects are executed and implemented, initially at the funded pilot centers and then more broadly across 

the Cancer Centers, Specialized Programs of Research Excellence, new NCI research initiatives, and intramural 

research programs. 

The caBIG pilot effort strives to: 

Maintain the current momentum of the informatics efforts at NCI. 

Create tools and systems that are adaptable to different institutional settings, meet Food and Drug 

Administration compliance requirements, and can retrieve common information important to biomedical 

research from existing biomedical information systems. 

Involve all Cancer Centers through updates of progress and solicitation of comments and feedback, 

while working directly with a few Centers for pilot development. 

Resources 

existing infrastructure, and development priorities. New tools and infrastructure 

will be deployed at test sites. Feedback gathered during the pilot will drive 

improvement priorities. Finally, the tools and infrastructure will be fully deployed 

to the cancer center community. 

98 The Nation’s Investment in Cancer Research 
A Plan and Budget Proposal for Fiscal Year 2005 99

E N A B L E R S O F D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY

From primary prevention to survivorship or end-of-life care, communication provides people with the

vital link to the information they need to make good decisions. Effective communication motivates

people and communities to take actions that reduce their cancer risk. It can be used to encourage

people to eat healthy, wear sunscreen, exercise regularly, stop smoking, and get screened for cancer.

In every cancer diagnosis, communication plays a key role in helping patients and physicians with 

the information they need to make the best decisions about treatment options, risks, and benefits.

And those who live beyond cancer experience a better quality of life when they have access to information and support in dealing with post-treatment effects. Culturally and linguistically appropriate

communication helps people make decisions that are compatible with their values and beliefs. 

Yet research reveals substantial gaps between the information people want and need

and what they receive. The explosion in information delivery systems such as the

Internet has given people access to information from any number of sources, but the

inconsistent quality and reliability of the information jeopardizes the ability of

patients and their caregivers to sort out which information to use in making critical, sometimes lifesaving, decisions. Research shows that people perceive information based on their prior knowledge, beliefs, and experiences. America’s increasing

cultural diversity and a pervasive pattern of disparities that limit access to and use

of information only add to the complexities of effective cancer communications. 

NCI is committed to helping Americans better understand news about cancer — whether

the news comes in the form of a diagnosis, media report, or Website communication. A

better understanding of cancer improves communications between patients and healthcare

professionals and helps them work together to make good decisions and minimize inappropriate ones. NCI promotes cancer prevention and detection through communication

activities that provide the information, tools, and encouragement people need to embrace

actions known to reduce cancer risk. We also promote the use of age-appropriate 

cancer screening and early detection tests — e.g., mammograms, Pap tests, and colorectal

cancer screening tests. People who are empowered with knowledge can make informed

decisions about treatment, disease management, palliative care, and end-of-life options.

PROGRESS IN PURSUIT OF OUR GOAL

Increasing Knowledge through Discovery 

The Centers of Excellence in Cancer Communications Research (CECCRs) serve as the

centerpiece of NCI’s communications research. The Centers foster the advancement 

of cancer communication science by examining the processes and mechanisms

through which communication plays a role in cancer control. Four centers were

funded in July 2003 to carry out a variety of projects such as facilitating information seeking related to prostate, breast, and colorectal cancers; developing decision

aids concerning tamoxifen use among women at high risk for breast cancer; 

promoting fruit and vegetable intake among African Americans; examining media

coverage of cancer-related issues in African American newspapers; and developing

and evaluating new interactive health communication systems. 

Cancer Communications

Discovery 

NCI actively pursues research

to examine the processes 

and mechanisms through

which cancer information is

delivered, understood, and

used. Specific initiatives focus

on such topics as cancer 

risk perception, information

processing, and decision

making. The knowledge

gained allows us to develop,

evaluate, and deliver communication resources and interventions. 
Development 

NCI has taken an important 

first step in bridging the gap 

between development and 

delivery by funding grant supplements for investigators to 

disseminate promising interventions and products to the 

broader population. The first 

seven supplements address 

sun safety, 5 A Day promotion, 

smoking cessation, dietary 

patterns in preschool children, 

cancer screening, interventions for use in managed care 

settings, and interventions for 

underserved populations. 

Delivery 

As a first step toward understanding the nature, extent, and depth of media 

coverage on cancer, NCI is conducting a pilot study to examine how news media 

reported the 2002 controversy on the efficacy of mammography in saving lives. An 

analysis of news stories published in the Nation’s top 50 newspapers will reveal 

how reporters framed the controversy in terms of risks and benefits and which 

sources, among scientists and the advocacy community, were used in reporting the 

debate. This study will serve as a complement to surveys that assessed women's 

reactions to the controversy. Both media content analysis and surveys will help NCI 

understand how media coverage of cancer could influence audience perceptions of 

risk and risk-related behaviors. The findings will enable NCI to take appropriate 

actions to influence people’s risk behaviors as well as proactively work with the 

media to provide accurate and timely information on cancer. These studies will also 

help inform future communications planning. 

Developing and Evaluating Communication Resources and Interventions 

To promote increased participation in cancer clinical trials, NCI developed a Webbased course for health professionals, Incorporating Clinical Trials into Your 

Practice. The course emphasizes the importance of health professional participation 

in clinical trials, either through referral or by becoming a clinical trials investigator, 

and provides practical information and guidance on conducting and locating trials. 

It complements NCI's Clinical Trial Education Series (CTES), a set of 13 educational resources designed to educate health care professionals and the public 

(cancer.gov/clinicaltrials/resources/clinical-trials-education-series). Course participants

may receive Continuing Medical Education credits for course completion. 

NCI held a workshop on health behavior theories in May 2002 to examine actions 

individuals can take to prevent cancer and speed its early detection. A group of 

experts with backgrounds in risk communication, risk behaviors, cancer screening, 

diet, and tobacco addiction discussed how our understanding of health behaviors 

can be improved in order to help inform health interventions. 

Partnering to Deliver Evidence-Based Cancer Interventions 

NCI encourages all Americans to eat 5 to 9 servings of fruits and vegetables a day 

for better health. This advice is especially critical for African American men, who 

suffer a disproportionately high incidence of and mortality from many chronic diseases related to diet, including cancer. In 2003, NCI launched a 9 A Day campaign for 

African American men. The campaign includes national radio programming on more 

than 230 affiliate urban stations through a faith-based initiative, and outreach and 

partnership opportunities with national African American organizations and television programming outlets. In a related campaign, a National Basketball Association 

sports celebrity helped NCI spread the message to all men to “Shoot for 9” via public service announcements and media interviews that aired during the 2003 playoffs. 

For more information, go to 9aday.cancer.gov and 5aday.gov/shootfor9. 

100 The Nation’s Investment in Cancer Research 
powerful communication 

arms is the 

Cancer Information 

Service (CIS). 

One of NCI’s most 

CIS helps people become 

active participants in their 

health care by providing the 

latest scientific cancer information in understandable 

language. Through a network 

of 14 regional offices located 

at Cancer Centers or major 

medical centers throughout 

the country, CIS serves the 

entire United States, Puerto 

Rico, the U.S. Virgin Islands, 

and the U.S. Territories. In 

2002, CIS handled over 1.4 

million requests for service 

from patients, their families, 

the general public, and 

health professionals. The 

Cancer Information Service 

offers smoking cessation 

assistance (1-877-44U-QUIT), 

cancer-related publications, 

and recorded information 

about cancer 24 hours a day, 

7 days a week (1-800-4-CANCER). In addition, through 

its Partnership Program, CIS 

collaborates with national, 

state, and regional organizations to develop appropriate 

cancer education programs 

for minority and medically 

underserved populations. 

MPCAI in a unique public-private partnership with the Centers for Medicare and 

Medicaid Services (CMS) and the National Asian Women’s Health Organization, 

NCI adapted, tested, and disseminated nationally an Asian American/Pacific 

Islander (AAPI) mammography education resource. Developed for Chinese, 

Vietnamese, and Pacific Islander women in their 40s and older, this breast health 

screening brochure was adapted from CMS-funded intervention research. NCI collaborated with five AAPI community organizations to pilot test this educational 

resource. A multipronged distribution strategy focused on 10 U.S. geographic areas 

with the largest concentrations of AAPI populations. Evaluation of the distribution 

strategy is underway. 

With the newly revised Making Health Communications Programs Work: 

A Planner’s Guide, NCI has provided a resource for health communicators that 

emphasizes a practical approach to the communications process and reflects recent 

advances in knowledge and technology such as the Internet. This highly popular 

publication has been an essential communications tool for many professional associations, private organizations, and government agencies. Communicators can use 

the Guide to assess community needs, create messages, identify appropriate audiences and media, conduct market research, create partnerships, and evaluate and 

improve programs. 

Research Tested Intervention Programs (RTIPs), a collaboration between NCI 

and the Substance Abuse and Mental Health Services Administration, was 

launched as part of the Web portal, Cancer Control PLANET. RTIPs provide 

access to examples of evidence-based intervention programs and products developed and evaluated by researchers in the field. Cancer Control PLANET provides 

access to data and resources that can help cancer control planners, program staff, 

and researchers design, implement, and evaluate evidence-based cancer control 

programs. (See also page 85.) 

U.S.- and U.K.-

The International Cancer Research Portfolio Web site (www.cancerportfolio.org) was 

launched in June 2003 to provide public access to information about approximately 

13,000 cancer-related research projects. The project is the result of collaboration 

among the NCI, the Congressionally Directed Medical Research Programs of the 

Department of Defense and the National Cancer Research Institute of the United 

Kingdom. This new online resource allows scientists, patient advocates, and the 

public to search and browse research portfolios of U.S. and U.K. cancer research organizations by specific 

cancer and type of cancer research, providing information about the funding organization, awardee institution, 

and principal investigator along with a detailed research abstract. 

New Online Tool Puts 

Sponsored Cancer 

Research Information at 

Your Fingertips 

E N A B L E R S O F D I S C O V E R Y, D E V E L O P M E N T, A N D D E L I V E R Y 

A Plan and Budget Proposal for Fiscal Year 2005 101 
CANCER COMMUNICATIONS 

GOAL Objectives and Fiscal Year 2005 Milestones and Required Funding Increases 

Understand, apply, Discovery 

and disseminate 1. Increase knowledge about cancer information needs, beliefs, decision making 

effective communica- processes, and behaviors, and the relationships between these factors among 

tion approaches that different publics, including general populations, the underserved, patients and 

their caregivers, high-risk groups, and health providers.	 $12.50 M maximize access to 

and appropriate use ■ Investigate and monitor the commercial communication, consumer technology, and health technolof cancer information ogy industries to identify developments that are likely to influence access to, the means for, and the 

effectiveness of cancer-related communication 3 to 10 years into the future. $0.50 M by all who need it. 

■ Identify the information, communication, and decision making factors related to the etiology of 

cancer disparities, and develop an evidence base to support population-specific strategies for 

overcoming cancer disparities. $2.50 M 

■ Analyze data from a variety of sources, including the Health Information National Trends Survey 

(HINTS) to understand public knowledge, attitudes, beliefs, and information-seeking behaviors related to cancer and screening practices, with an oversampling of underserved groups. $2.00 M 

■ Investigate high-priority cancer communication issues among different population subgroups on 

such issues as risk communication, health literacy, informed decision making, provider-patient 

communication, perceptions of cancer clusters, communication of cancer statistics, perceptions of 

cancer as a chronic disease, the information needs of cancer patients as they undergo and recover from various treatment modalities, exit communication strategies for patients who are leaving 

clinical trials, and perceptions and practices of various population groups with regard to genetic 

testing for cancer. $4.00 M 

■ Examine the fundamental processes and mechanisms of cancer communication science through 

continued funding of the Centers of Excellence in Cancer Communications Research (CECCRs). 

■ Analyze NCI’s intramural clinical trials recruitment methods to develop a model for Phase I and II 

clinical trials recruitment and follow-up care. $0.75 M 

■ Identify how various population groups understand recommendations on diet, physical activity, and 

weight for the purpose of informing the development of communication programs. $2.00 M 

■ Survey health and science journalists to understand contemporary methods and strategies used in 

health reporting. $0.75 M 

Development 

2.	 Develop and evaluate communication resources and interventions for use in 

reducing the cancer burden, including overcoming barriers to access and 

completion of cancer treatment, particularly among underserved populations. $18.50 M 

■ Study the nature of information provided to different audiences through various media and the availability of these media to underserved communities and individuals. Measure the public’s response 

to cancer information in the media through development of a Cancer Information Surveillance 

System (CISS). $4.00 M 

■ Establish and apply methods to ensure that communication tools, products, and programs used by 

NCI and its partners are evidence-based. These methods will include syntheses of research, 

consumer research, product development research, and systematic evaluation. $3.00 M 

■ Complete the development of HINTS as a public access database for research and program planning, 

and expand HINTS to include a survey of cancer survivors. $1.00 M 

102 The Nation’s Investment in Cancer Research 
■ Evaluate the effectiveness of the CIS in increasing the public’s knowledge of cancer topics and positively influencing healthful behaviors and decisions. $2.00 M 

■ Evaluate CIS partners for satisfaction with collaboration, success at reaching underserved populations, and organizational capacity to disseminate cancer information. $1.00 M 

■ Foster a more integrated and coordinated approach to media campaigns across NIH and in partnership with other Federal agencies, such as the Centers for Disease Control and Prevention, to 

develop important behavioral messages on health issues that cross multiple diseases. $1.50 M 

■ Cultivate relationships with the commercial communication, consumer technology, and health technology industries to foster improved access to and provision of effective cancer-related information, 

including decision making aids. $2.00 M 

■ Partner with advocacy groups, state health departments, and other Federal agencies to develop a 

strategy to help the public understand cancer clusters and to assist partners in communicating 

effectively about the issue. $2.00 M 

■ Collaborate with organizations to support and evaluate the outcomes of promoting accurate cancer information messages in popular culture (e.g., movies and television shows). $2.00 

Delivery 

3.	 Engage with partners and the media to deliver evidence-based cancer interventions in clinical and public health programs. $10.50 M 

■ Support dissemination research to identify optimal means for NCI and grantees to increase the 

adoption of NCI-funded evidence-based interventions. $3.00 M 

■ Facilitate the media’s effective use of NCI’s resources (for example, statistical reports) through outreach including annual workshops and toolkits. $1.00 M 

■ Translate findings and lessons learned from large prevention trials into key messages, tools, and 

products that can be used to inform and educate the public about cancer prevention. $1.50 M 

■ Strengthen collaborations with Federal agencies and other organizations to further reduce the burden of highly preventable cancers such as colorectal and lung cancers. $2.00 M 

■ Expand the dissemination of NIH and NCI grant resources, policies, and funding opportunities to 

the extramural scientific community engaged in cancer research. $2.00 M 

■ Expand efforts to communicate research findings to the public via the news media, using strategies 

and tools that reach ethnically diverse populations. $1.00 

Management and Support $ 2.00 M 

Total $43.50 M 

E N A B L E R S O F D I S C O V E RY, D E V E L O P M E N T, A N D D E L I V E RY 

A Plan and Budget Proposal for Fiscal Year 2005	 103 
Index of Selected Topics* 

aging and cancer, 

7, 9, 20, 64-65, 67, 68 

AIDS and cancer, 

xix, 8, 19, 29, 60 

alcohol and cancer, 

xii, 10, 39, 60 

bladder cancer, 

7, 10, 18, 23, 36, 38, 

40, 52, 65 

brain tumors, 

xiii, 11, 14, 40, 65 

breast cancer, 

xii, xiv, xxi, 10, 11, 13, 14, 

15, 16, 17, 18, 19, 20, 23, 

24, 25, 26, 27, 34, 36, 40, 

45, 46, 47, 50, 52, 53, 54, 

56, 59, 60, 65, 67, 69, 80, 

84, 85, 88, 89, 99, 101 

cervical cancer, 

19, 23, 29, 35, 36, 38, 40, 

53, 54, 56, 59, 60, 62, 74 

chemotherapy, prevention 

and treatment, 

xiv, xv, xviii, xix, 8, 23, 25, 

27, 29, 30, 41, 42, 46, 55, 

67, 69, 75, 86, 87, 88, 89. 

See also targeted interventions. 

childhood cancers, 

xv, xviii, 8, 19, 27, 34, 47, 

49, 50, 51, 66, 68, 69, 70, 

78, 87, 90, 100 

colorectal cancers, 

xii, xx, 10, 11, 14, 15, 22, 

23, 27, 28, 39, 40, 45, 46, 

47, 50, 52, 53, 54, 55, 58, 

60, 65, 84, 87, 89, 99, 103 

diet and cancer, 

xii, xiii, xxi, xx, 2, 3, 11, 27, 

29, 39, 45-50, 60, 61, 71, 88, 

99, 100, 102 

endometrial cancer, 

46, 89 

energy balance and cancer, 

9, 14, 45-50 

esophageal cancer, 

xv, xvi, xxi, 23, 38, 40 

Ewing’s sarcoma, 

exercise and cancer, 

xxi, 2, 45-50, 60, 71, 99, 102 

gastrointestinal cancers, 

18, 22, 80, 81. See also colorectal cancers, gastrointestinal stromal tumors, stomach 

cancer. 

gastrointestinal stromal tumors, 

xix, 87 

gene expression array, 

xv, xvi, 17, 18, 73 

genomics, 

xv, 12, 14, 18, 24, 26, 

28, 39, 42 

head and neck cancer, 

23, 36, 87. See also laryngeal 

cancer, mouth cancer, oral 

cancers, pharyngeal cancer. 

idiopathic hypereosinophilic 

syndrome, 

xix 

immune system and cancer, 

xiv, xvii, 8, 19, 20, 26, 27, 

29, 32, 71, 75 

kidney cancer. 

See renal cancer. 

laryngeal cancer, 

38, 40 

leukemia, 

xiv, xviii, xix, 19, 27, 34, 38, 

40, 65, 69, 75, 84, 87, 89 

liver cancer, 

xvi, 19, 22, 23, 38 

lung cancer, 

xii, xiv, xvii, 17, 18, 23, 26­

28, 33, 34, 38-42, 52, 58, 60, 

65, 81, 89, 103. See also 

tobacco and cancer. 

lymphoma, 

xix, 11, 14, 19, 25, 27, 29, 

52, 65, 67, 69, 75, 84, 89 

melanoma, 

xii, xvi, xvii, 11, 14, 26, 

30, 89 

microenvironment. 

See tumor microenvironment. 

minorities and cancer, 

xii, xviii, 15, 24, 30, 40, 42, 

47, 58-63, 67, 69, 71, 79, 82, 

83, 86, 91, 99, 100, 101, 103 

molecular profiling of 

genes and proteins, 

10, 11, 17, 18, 66, 84, 85. 

See also gene expression 

array, proteomics. 

molecularly targeted 

interventions, 

xix, 2, 3, 16, 18, 21, 24-28, 

30, 31, 32, 40, 78, 86, 87, 

88, 89 

mouth cancer, 

8, 40 

myeloma, 

20, 85, 89 

nanotechnology, 

xvii, 11, 18, 20, 24, 32, 

35, 36 

nasal cancers, 

38 

nervous system cancers, 

xviii, xix, 8 

neuroendocrine cancers, 89 

neuroectodermal tumor, 8 

nutrition and cancer. See diet 

and cancer 

obesity/overweight and cancer, 

xxi, 2, 9, 42, 45-50, 60, 

69, 102 

oral cancers, 

18, 38 

ovarian cancer, 

xiv, 11, 13, 14, 17, 18, 26, 

39, 56, 65, 85 

pancreatic cancer, 

xviii, 11, 15, 17, 23, 28, 

38, 40, 65 

pediatric cancers. 

See childhood cancers. 

pharyngeal cancer, 

38 

physical activity and cancer. 

See exercise and cancer. 

progress review groups (PRGs), 

6- 8, 37, 61, 62, 73, 74, 

77, 85 

prostate cancer, 

xii, xiii-xiv, xvii, 6, 10, 11, 

14, 15, 16, 17, 18, 20, 27, 

28, 34, 36, 39, 45, 46, 47, 

50, 52, 53, 58, 60, 65, 81, 

85, 89, 99 

proteomics, 

xv, 17, 18, 21, 24, 26, 28, 29, 

42, 48, 85, 88, 92. See also 

molecular profiling of genes 

and proteins. 

Radiation, research and therapy, 

xiii, xiv, xv, xvii, xviii, 26, 

29, 30, 31, 35, 58, 65, 69, 

75, 86, 87, 89, 90 

renal cancer, 

11, 24, 38, 40, 45, 50, 84, 89 

sarcomas, 

xiv, 8, 19, 29, 69, 89 

skin cancers, 

23. See also melanoma. 

socioeconomic status 

and cancer, 

xviii, 9, 40, 58, 60, 62, 67 

stomach cancer, 

23, 38, 40, 58, 65 

surgery, 

xiv, xvi, xvii, xviii, xx, 15, 

23, 31, 39, 40, 65, 86, 87 

testicular cancer, 

11 

thyroid cancer, 

xiv, xvi 

tobacco and cancer, 

xii, 2, 3, 4, 9, 10, 14, 22, 

33, 38-45, 49, 53, 60, 69, 

71, 81, 99, 100, 101 

tumor microenvironment, 

2, 3, 9, 16-21 

vaccines and cancer, 

xvii, 19, 26, 27, 28-29. 

* See also Table of Contents on 

page v for major topics covered 

in this document. 

The Nation’s Investment in Cancer Research 

8 

104 
Glossary


allele — Any of the alternative 

forms of a gene that are located 

together on a chromosome. For 

autosomal chromosomes, each 

allele will normally have two 

copies of the same gene, one 

inherited from the mother and 

one from the father. 

angiogenesis — Growth of new 

blood vessels. 

antibody — A type of protein 

made by certain white blood cells 

in response to a foreign substance 

(antigen). Antibodies bind to the 

antigen and either destroy the foreign substance directly or make it 

easier for the body to do so. 

antigen — A foreign substance 

that causes the immune system to 

make a specific immune response. 

apoptosis — A type of cell death 

where the cell is “programmed” 

to “commit suicide” when it has 

been sufficiently damaged or is no 

longer needed. 

autosomal — Pertaining to a 

chromosome not involved in sex 

determination. 

autosomal dominant — Requires 

that only one affected parent have 

the trait to pass it to offspring. 

biomarker — A substance sometimes found in the blood, other 

body fluids, or tissues that can 

be used to assess the presence 

of cancer. 

biosensor — A type of biomolecular probe that measures the presence or concentration of biological 

molecules, biological structures, 

etc., by translating a biochemical 

interaction at the probe surface 

into a quantifiable physical signal 

such as light or electric pulse. 

biospecimen — Sample taken 

from a patient such as blood, 

tissue, urine, or sputum. 

cachexia — The loss of body 

weight and muscle mass frequently seen in patients with cancer, 

AIDS, or other diseases. 

candidate gene — A gene 

researchers suspect may be related 

to a certain condition, such as 

cancer. 

case-control study — An epidemiological study in which the risk 

factors of people with a certain 

disease (cases) are compared 

with those without the disease 

(controls). 

cell line — Cells of a single type 

taken from an animal or human 

and grown in the laboratory. 

cohort study — A research study 

that compares a particular outcome, such as lung cancer, in 

groups of individuals who are 

alike in many ways but differ 

by a certain characteristic — for 

example, female nurses who 

smoke compared with those 

who do not smoke. 

combinatorial chemistry — The 

systematic creation of large 

numbers of small molecules in 

“libraries” that can be screened in 

vitro for potential as cancer drugs. 

comparative genomic hybridization — A method of identifying 

and mapping differences in DNA 

sequencing data between normal 

cells and tumor cells. 

computer adaptive data collection/testing — A computer 

administered test that tailors the 

content of the test to the skills 

of the test taker. 

correlative study — A type of 

study that tests for a relationship 

between a condition and a potential causal factor of the condition 

— e.g., cancer and obesity. 

cytotoxic — Cell killing. 

deregulated pathway — A molecular pathway that is not regulated 

in a normal manner by the cell. 

dietary crucifer — Any of a family 

(Cruciferae) of plants including 

cabbage, broccoli, cauliflower, 

brussels sprouts, and greens such 

as mustard greens. 

DNA — Deoxyribonucleic acid. 

The molecule that encodes genetic 

information in the nucleus of cells. 

It determines the structure, function, and behavior of the cell. 

dopamine — A neurotransmitter 

and hormone. Dopamine levels 

have been associated with mood 

state. 

enzyme — A protein that speeds 

up chemical reactions in the body. 

epidemiology — The study of the 

patterns, causes, and control of 

disease in groups of people. 

epigenetic effects — Changes in 

cellular biochemistry that influence the phenotype produced from 

a genotype. Epigenetic effects differ from genetic effects, which are 

caused by DNA mutation. 

epithelium — The thin layer of 

tissue that covers organs, glands, 

and other structures within the 

body. 

etiology — The study of the cause 

or origin of disease. 

expression — The process by 

which a gene’s coded information 

is converted into the structures 

present and operating in the cell. 

extracellular matrix — Any material produced by cells and secreted 

into the surrounding medium. 

fibroadenoma — A benign solid 

growth, usually found in the 

breast. 

fibrosis — The formation of 

fibrous tissue. 

functional genomics — Study of 

the function of individual genes 

and interactions among groups 

of genes to address biological 

questions. 

functional imaging — Sometimes 

called molecular imaging. Imaging 

techniques for detecting molecular 

signals that indicate the presence 

of biochemical activity and 

changes, such as cell growth or 

death. 

gene variant — A gene that is 

essentially the same as another, 

but has mutational differences. 

genetic profile — DNA analysis 

of a person’s body tissue or body 

fluid. 

genome — The complete genetic 

material of an organism. 

genotype — Referring to the 

genetic constitution (makeup) of 

an individual or group. 

genotyping — Measuring features 

of an individual’s genotype — e.g., 

testing for genetic mutations. 

germline — The body’s reproductive cells (egg or sperm). Germline 

DNA becomes incorporated into 

the DNA of every cell in the body 

of offspring. 

haplotype — A group of alleles 

of different genes that are linked 

closely enough to be inherited as 

a unit. 

histology — The study of cells and 

tissues at the microscopic level. 

histone — A type of protein found 

in chromosomes that help give 

them their shape and help control 

the activity of genes. 

hyperplasia — An abnormal 

increase in the number of cells in 

an organ or tissue. 

immune-mediated benefit — 

A benefit that results from activity 

of the immune system — e.g., 

mobilization of white blood cells 

against cancer cells. 

immunotoxin — An antibody 

linked to a toxic substance. Some 

immunotoxins can bind to cancer 

cells and kill them. 

in silico analysis — Analysis 

performed using computers in 

conjunction with informatics 

capabilities. 

in vitro — In the laboratory 

(outside the body). 

in vivo — In the body. 

late effect — Side effects of cancer 

treatment that only become apparent with long-term monitoring of 

the patient. 

ligand — Any molecule that binds 

to another; usually a soluble molecule such as a hormone or neurotransmitter that binds to a protein 

receptor. 

longitudinal study — A study that 

involves the repeated observation 

or examination of a set of subjects 

over time with respect to one or 

more study variables. 

lymphedema — A condition in 

which excess fluid collects in tissue 

and causes swelling. 

GLOSSARY 

A Plan and Budget Proposal for Fiscal Year 2005 105 
MAO-B inhibitor — A type of 

drug that inhibits the function of 

the enzyme, monoamine oxidase 

B. MAO-B inhibitors are commonly used to treat depression 

and Parkinson’s disease. 

methylation — The addition of a 

chemical group (methyl) to DNA 

that epigenentically alters gene 

expression. 

microarray — A powerful technology that allows simultaneous 

measurement of expression levels 

for up to tens of thousands of 

genes. 

microdissection — Dissection of 

tissues under a microscope. 

microenvironment — Local and 

systemic architecture surrounding 

a cancer cell. Includes other cells, 

growth factors, enzymes, and 

parts of the blood and lymphatic 

systems. 

microsatellite – A repetitive stretch 

of short DNA sequences that 

occur in increased numbers in cancer cells. 

molecular beacon — A type of 

biosensor that emits a signal, such 

as light, when it encounters a particular feature, such as a particular 

type of protein. 

molecular epidemiology — 

Epidemiology that focuses on 

measurements of molecular features. 

molecular imaging — See 

“functional imaging.” 

molecular signature — 

Characteristic features of the 

molecular composition of a 

cell or its surroundings. 

molecular target — Molecular 

features in a cancer cell or its 

surroundings critical to cancer 

development or progression that 

can potentially be disrupted to 

prevent or treat the disease. 

monoclonal antibody — 

Laboratory-produced protein that 

can locate and bind to a particular 

feature of cancer cells in the 

body. Monoclonal antibodies can 

be used to deliver drugs, toxins, 

or radioactive material directly to 

a tumor. 

mucinous — Pertaining to cells pharmacology — The study of 

that line certain internal organs the properties and reactions of 

and produce mucin (the main drugs, especially with relation to 

component of mucus). their therapeutic value. 

multimodal therapy — Therapy phenotype — The visible or 

that combines more than one measurable properties of an 

method of treatment. organism that are produced by the 

mutation — A permanent change interaction of the genotype and 

in the genetic material, usually in the environment — e.g., eye color. 

a single gene. polymorphism — Common variamycochemical — A chemical tion or mutation in DNA, not 

derived from fungi. always harmful. 

nanometer — A metric unit of process measure — An index of 

measure. Approximately 25.4 mil- the degree to which a service or 

lion nanometers equal one inch. procedure is performed correctly 

and appropriately; that is, the nanoparticle — Small clusters of service or procedure’s likely bene- atoms about 1 to 100 nanometers fit exceeds its likely harms or risks. long. proof of principle study — A study nanotechnology — Technology that demonstrates an agent to development at the atomic, molec- have the desired biological effect ular, or macromolecular range of	 on its target. approximately 1-100 nanometers 

to create and use structures, prospective study — A study in 

devices, and systems that have which participants are identified 

novel properties. and then followed forward in 

time. neoplastic — Abnormal and 

uncontrolled cell growth. proteasome inhibitor — Drugs 

that block the action of protea- nicotinic acetylcholine receptor — somes, cellular complexes that A type of neurotransmitter recep- break down proteins. tor in the hippocampus (a part of 

the brain) that naturally responds proteomics — The comprehensive 

to acetylcholine.	 study of proteins and their 

functions. nucleotide — Molecules that comprise the building blocks of DNA. quantum dots — Tiny crystals 

that glow when stimulated by 

oncogene — A gene that normally ultraviolet (UV) light; an in vivo directs cell growth, but is altered application of nanotechnology. to promote or allow uncontrolled 

cellular growth. radiolabeled — Labeled for detection with a radioactive material. 

open-source — Of or relating to 

source code (e.g., computer code) radiotracer — A radioactive 

that is available to the public. substance that can be traced in 

the body. patient navigation — The recruitment and training of persons from reference clone — The sequence 

underserved communities to assist for a particular gene that is 

in navigating patients through accepted as the true sequence. 

standard cancer diagnosis and resequencing — A specific applicatreatment services. tion of gene sequencing that prepeptide — Any compound consist- cisely determines the sequence of 

ing of two or more amino acids, bases in DNA. Resequencing is 

the building blocks of proteins. used to identify single nucleotide 

polymorphisms (SNPs). pharmacogenomics — The study 

of individual genetic differences in retrospective analysis — A study 

response to drug therapy.	 that looks backward in time, 

usually using medical records 

and interviews with patients who 

already have or had a disease. 

The Nation’s Investment in Cancer Research 

RNA — Ribonucleic acid, one 

of the two types of nucleic acids 

found in all cells. (The other is 

DNA.) RNA transmits genetic 

information from DNA to 

proteins produced by the cell. 

RNAi — RNA inhibitor. 

sequencing — Determination of 

the order of nucleotides in a DNA 

or RNA molecule or the order of 

amino acids in a protein. 

single nucleotide polymorphism 

(SNP) — A genetic change that is 

caused by substitution of a single 

nucleotide. 

stem cell — A cell from which 

other types of cells can develop. 

stroma — The supporting connective tissue of an organ. 

suicide genes — Genes that, when 

expressed, cause cell death 

through apoptosis. 

surrogate biomarker — A biomarker used to assess a surrogate 

endpoint. 

surrogate endpoint — A laboratory measurement of some biological indicator of a drug’s effectiveness, used in place of longer-term 

outcome measures. 

survey item bank — A collection 

of commonly used questionnaire 

items and scales. 

telemedicine — Delivery of health 

services via remote telecommunications. 

toxicology — The study of the 

chemistry and effects of poisonous 

substances and the treatment of 

poisoning. 

vascularization — Formation of 

blood vessels. 

von Hippel-Lindau syndrome — 

A rare inherited disorder in which 

blood vessels grow abnormally in 

the eyes, brain, spinal cord, adrenal glands, or other parts of the 

body. People with this syndrome 

have a higher risk of developing 

some types of cancer. 

well-differentiated — A tumor 

which is superficially similar in 

appearance to the parent tissue. 

yttrium — A rare elemental metal. 

A radioactive form of yttrium is 

used in radiation therapy and 

some types of immunotherapy. 106 
Acknowledgments


Each year, countless people at NCI; on our advisory boards; and in research, other professional, and 

advocacy organizations around the country provide their insights, perspectives, and expertise for the 

development of this document. Members of the Office of Science Planning and Assessment provide 

leadership and guidance for plan development from conceptualization to production. They work alongside 

the core group of NCI leaders who serve as Champions for the various priority areas and with staff of the 

Office of Budget and Financial Management and the Office of Communications. Numerous other people at 

NCI contribute information, review drafts, and identify new areas of emphasis. 

The following people made major contributions 

to this document: 

NCI Office of Science Planning and Assessment: Lead Staff:


Cherie Nichols, Kathie Reed, Kathy Sorrow, and Marianne


Kost. Priority Area Contacts: Anne Tatem, Jane Lockmuller,


Lisa Stevens, Samir Sauma, and Margaret Ames


NCI Priority Area Champions: Jeff Abrams, Rachel Ballard-


Barbash, Carl Barrett, Linda M. Brown, Martin Brown, 


Ken Buetow, Neil Caporaso, Nelvis Castro, Steve Chanock,


Michaele Christian, Norm Coleman, Jim Crowell, Bob Croyle,


Ellen Feigal, Michele Forman, Harold Freeman, Paulette Gray,


Lee Helman, Bob Hoover, Lenora Johnson, Gary Kelloff, 


Jon Kerner, Brian Kimes, Scott Leischow, Joe Lipscomb, 


Ed Maibach, Mary McCabe, John Milner, Lori Minasian, 


Julia Rowland, Ed Sausville, Arthur Schatzkin, Jeff Shilling,


Dinah Singer, John Sogn, Bob Strausberg, Dan Sullivan, 


Ed Trapido, and Vish Viswanath


NCI Office of Budget and Financial Management: 

Jim Dickens and Ngan Nguyen 

NCI Office of Communications: Jo-Ann Kriebel, 


Tamara Maze-Gallman, Donna Bonner, Paul LaMasters, and


Diane Reid


NCI Office of the Director: John Hartinger and Jim Mathews 


Other NCI offices: Jane Daye, Matt Fritts, Elisabeth Handley,


Jill Johnson, and Stacey Vandor


Michigan State University: Barbara Given, Charles Given, 


and Paula Sherwood


Other contributors include: 

NCI Staff: Alan Rabson, Noreen Aziz, Ann Barker, 


Joseph Fraumeni, Peter Greenwald, Norma Davis, 


Kevin Callahan, Anna Levy, Jim Corrigan, Marilyn Duncan,


Buddy Clark, Lauren Christopher, Christine Moretto, 


Julie Schneider, Kevin Wright, Heather Burns, Michelle


Bennett, Kelly Blake, Barbara Croft, Gregory Downing,


Andrea Denicoff, Kay Flemming, Dorothy Foellmer, 


Barbara Galen, Neil Goldman, Lakshmi Grama, 


Ernie Hawk, Steve Hazen, Marianne Henderson, 


Steven Hewitt, John Hoffman, Jim Jacobson, Diana Jeffery,


Kathy Kelly, Geoffrey Kidd, Lance Liotta, Guoying Lui, 


Cheryl Marks, Anne Menkens, Suresh Mohla, Ed Monachino,


Kathleen Schlom, Sudhir Srivastava, James Tatum, 


Sheila Taube, Gina Tesauro, Tracy Thompson, 


Robert Yarchoan, Sheila Zahm, and Katherine Zoon. 


National Institute on Aging: Rosemary Yancik. 


University of Pennsylvania: Gillies McKenna. University 


of Michigan: Theodore Lawrence. M. D. Anderson Cancer


Center: Michele Follen


The following people and organizations provided input 

prior to the development of this document. 

NCI Director’s Consumer Liaison Group: Vernal Branch,


Kathy Giusti, Ruth Lin, Barbara LeStage, Gena Love, 


Michael Katz, Karen Packer, Nyrvah Richard, Doug Ulman,


and Marisa Weiss


NCI-Designated Cancer Centers: Dave Alberts, 


Ralph Freedman, Gary Giovino, and John Mendelsohn


Professional and Advocacy Organizations: American


Association for Cancer Research, American Society for


Clinical Oncology, American Society for Therapeutic


Radiology and Oncology, The Children’s Cause, and


Federation of Practice Based Research Networks


Individual Reviewers: Edith Balbach, Steve Booth-Butterfield,


Judith Brook, Gregory Connolly, Dave Haaga, Dorothy


Hatsukami, Bruce Hillman, Wendy Hobbie, Judy Hopkins,


Lawrence Hunter, Ferenc Jolesz, Herb Kressel, 


Nancy Krieger, Ed Lichtenstein, Pamela Ling, Ruth Malone,


Timothy Rebbeck, Barbara Stillwater, and Tom Vogt


A special thank you goes to the following people who 


provided writing, design, editing, proofing, and printing sup­


port for the production of this document: Suzanne Reuben of


Progressive Health Systems; Lynne Komai, Don Wheeler, and


Claudia Smith of The Watermark Design Office; Paula Zeller;


Kathy Hollen; and Walt Burroughs.


ACKNOWLEDGMENTS 

A Plan and Budget Proposal for Fiscal Year 2005 107 
Valuable World Wide Web Locations Cancer Information Service (CIS)

National Cancer Institute cancer.gov By phone 

National Institutes of Health www.nih.gov 1-800-4-CANCER (1-800-422-6237) 

Department of Health and Human Services www.hhs.gov For deaf and hard-of-hearing 1-800-332-8615 

Cancer Research Portfolio researchportfolio.cancer.gov 

International Cancer Research Portfolio www.cancerportfolio.org On the Web 

Cancer News newscenter.cancer.gov cis.nci.nih.gov 

Cancer Science newscenter.cancer.gov/sciencebehind 

This Document Online 

Access expanded content for this Plan and Budget Proposal, including links to key Websites, at plan.cancer.gov. 

Online links related to the chapters in this book include the following. 

National Agendas for Disease-Specific Research 

■ Progress Review Groups prg.cancer.gov 

■ Research Initiatives cri.cancer.gov 

Investigator-Initiated Research 

■ Research Portfolio researchportfolio.cancer.gov 

■ International Portfolio www.cancerportfolio.org 

■ Research Resources resresources.nci.nih.gov 

■ Funding www.cancer.gov/researchfunding 

Centers, Networks, and Consortia 

■ Cancer Centers www.cancer.gov/cancercenters 

■ SPOREs spores.nci.nih.gov 

National Clinical Trials Program 

■ Cancer Clinical Trials www.cancer.gov/clinicaltrials and 

www.cancer.gov/clinicaltrials/understanding 

Bioinformatics for Cancer Research 

■ Center for Bioinformatics ncicb.nci.nih.gov 

Genes and the Environment 

■ Family Registry epi.grants.cancer.gov/CFR 

■ Genetics Network epi.grants.cancer.gov/CGN 

Signatures and Microenvironment 

■ CGAP cgap.nci.nih.gov 

■ EDRN www.cancer.gov/prevention/cbrg/edrn 

■ Director’s Challenge dc.nci.nih.gov 

Molecular Targets 

■ Developmental Therapeutics dtp.nci.nih.gov 

■ Intramural Initiatives ccr.cancer.gov/initiatives 

Cancer Imaging and Molecular Sensing 

■ Biomedical Imaging www.cancer.gov/bip and 

www.cancer.gov/clinicaltrials/understanding/scienceexplained-imaging 

Cancer Communications 

■ Extraordinary Opportunity cancercontrol.cancer.gov/eocc 

Quality of Cancer Care 

■ Applied Research appliedresearch.cancer.gov 

Cancer-Related Health Disparities 

■ NCI Center crchd.nci.nih.gov 

Cancer Survivorship 

■ Survivorship Research survivorship.cancer.gov 

Tobacco and Tobacco-Related Cancers 

■ Tobacco Research tobaccocontrol.cancer.gov 

Research Training and Career Development 

■ Opportunities cancertraining.nci.nih.gov 

Emerging Trends in Cancer 

■ Progress Report progressreport.cancer.gov 

■ Mortality Maps www.cancer.gov/atlasplus 

■ SEER seer.cancer.gov 

Ordering this Document Telephone Assistance for Smoking Cessation 

By email cisocc@pop.nci.nih.gov 

By Internet www.cancer.gov/publications 

By phone 1-800-4-CANCER 

By fax 1-301-330-7968 

NCI provides telephone-based assistance for smokers who 

want to quit through the Cancer Information Service (CIS) 

at 1-800-4-CANCER. Callers can speak with someone in 

English or Spanish in the United States, Puerto Rico, the 

U.S. Virgin Islands, and territories in Guam and Saipan. 

Smoking cessation service representatives: 

■ Assess the caller’s individual smoking behavior. 

■ Provide brief educational messages. 

■ Help callers develop a personalized action plan 

for quitting. 

■ Reinforce the information with written materials. 

108 The Nation’s Investment in Cancer Research 
Our Challenge Goal to the Nation

Eliminate the suffering and death

due to cancer by 2015.
NIH Publication No. 03-5446 

October 2003