National Cancer Institute


The Nation’s Investment in cancer research


A Plan and 

Budget Proposal 

for Fiscal Year 

2006 

Prepared by 

the Director 

National Cancer 

Institute 

U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES 

National Institutes of Health 
When we as a Nation reach our Challenge Goal to eliminate the suffering 

and death due to cancer, it will be because we have been able to: 

■ Gain a more complete understanding of the causes of cancer and of the biological mechanisms of 

cancer initiation and progression. 

As we validate the multiple risk factors and improve our understanding of the full range of genetic 

and biological changes that lead to cancer, we will be able to use that information to develop more 

effective and tailored strategies for cancer prevention and control, early detection, diagnosis, 

treatment, and follow-up care across the spectrum of need. 

■ Make prevention our first line of defense against cancer. 

Tobacco control programs will help us prevent the 30 percent of U.S. deaths from cancer that are 

related to smoking. Effective strategies for reducing the incidence of obesity in our Nation could 

lower cancer death rates by as much as 14 percent in men and 20 percent in women and reduce 

the risk for several common cancers by up to 30 percent. Cancer prevention medicines, dietary 

supplements, and vaccines, which have been proven in clinical trials, promise to eliminate or delay 

the development or progression of cancer. 

■ Detect many cancers early enough to make successful treatment possible. 

Universal access to currently available interventions for screening and early detection of cervical, 

colorectal, and breast cancers will immediately improve patient outcomes. For example, the five-year 

survival rate for colorectal cancer is nearly 90 percent for early-stage local disease compared with 

9 percent for later-stage disease that has spread to distant organs. Diagnostics based on validated 

biomarkers will someday be used for the early detection of other cancers based on analysis of the 

protein patterns in a single drop of blood. 

■ Effectively eliminate many cancers. 

Improved care has already helped us cure some cancers. As we look to the future, molecularly 

targeted diagnosis and treatment will help us eliminate other cancers with minimal side effects. 

Innovative imaging technology will make diagnosis and treatment more accurate and less invasive. 

Nanotechnology promises to enable better diagnostic platforms and delivery systems for more 

precise therapies with far fewer adverse side effects. 

■ Manage other cancers as chronic diseases. 

New paradigm molecular approaches will enable us to control other cancers so that people can 

live productive, healthy lives in spite of their cancer. Our ability to monitor and validate healthcare 

patterns, interventions, and outcomes will inform decision makers and caregivers to ensure quality 

cancer care for all, including a growing population of patients over 65. 

■ Dramatically improve quality of life for cancer survivors. 

More and more people are benefiting from the medical advances that have improved both quality 

of life and length of survival for cancer patients. Evidence-based and culturally appropriate 

supportive care, symptom management, and rehabilitation will all help address the medical and 

psychosocial needs of survivors and their caregivers. 

The strategic investments described in this document provide vision and direction for the nationwide community of 

researchers, public health workers, healthcare providers, patients, advocates, and policymakers working to defeat cancer. 

To learn more about recent progress in these and other areas of NCI investment, please refer to The Nation’s Progress in 

Cancer Research: An Annual Report for Year 2004 to be published in early 2005. Go to cancer.gov for regular updates on 

cancer research and other activities of the National Cancer Institute. 
DIRECTOR’S MESSAGE 

Director’s Message 

Early in 2003, as the Director of the National Cancer Institute, I announced our Challenge Goal to 

the Nation – to eliminate the suffering and death due to cancer by 2015. Since that time, we at NCI 

have worked internally and with the national scientific, medical, and lay community to identify the 

critical elements required to reach this goal. Our proposed strategic investments for Fiscal Year 

2006 reflect our recognition that the only way we will achieve our Challenge Goal is to capitalize on 

the most promising opportunities, remove any barriers that might be impeding progress, and 

ensure that laboratory discoveries are validated in clinical trials and reach the patient or the person 

at risk for cancer. 

Exponential advances in cancer research are defining, with ever increasing specificity, the many 

genetic, molecular, and cellular events that influence the cancer process. We now understand 

cancer as an ongoing process that can be interrupted at many stages – from susceptibility to initiation to disease progression. We are translating this new knowledge into innovative, evidence-based 

strategies to prevent cancer from developing, eliminate it early when it does occur, and modulate its 

devastating effects. 

With the cancer Biomedical Informatics Grid (caBIG), we are using the power of information 

technology to connect all cancer researchers to data and analytical tools that will dramatically improve 

research efficiency. We are advancing imaging technologies to detect tumors early when they are 

easier to treat, to guide therapy or surgery, and to monitor in real time the molecular effects of 

therapeutic interventions. Image-guided interventions are used, not only to aid in the successful 

treatment of some cancers and precancerous lesions, but also to provide minimally invasive, well 

tolerated therapies that eliminate or transform cancers into well managed diseases. 

Recent advances in proteomics and the technology of mass spectrometry allow for unprecedented 

analysis of the body’s proteins to define the biomarkers of cancer. Identifying the proteins associated 

with cancers will allow us to employ recent advances in molecularly targeted imaging to locate very 

small tumors and interrogate their molecular features. Drugs attached to agents that seek out the 

proteins on cancer cells will direct therapy exactly where it is needed, without damage to surrounding 

healthy cells. 

We are also developing prevention drugs and vaccines. More easily administered strategies like 

these hold promise for tremendous benefit to people at high risk for certain types of cancer. For 

example, the cervical cancer vaccines now under development may ultimately save hundreds of 

thousands of lives around the world every year. 

Advances gained through cancer initiatives will translate into progress for other serious diseases as 

well. The new National Advanced Technologies Initiative for Cancer, for example, will build national 

scale public-private coordination that will have far reaching benefits for cancer as well as many other 

diseases. 

Our 2015 Challenge Goal is an urgent call to action that will require a concerted, collaborative effort 

by the entire community. At NCI, we believe that the Goal is within our grasp, and we are prepared 

to stretch the boundaries of science, imagination, and human will to achieve success. 

Andrew C. von Eschenbach 

October 2004 
2 THE NATIONAL CANCER INSTITUTE 

Eliminating the Suffering and Death Due to Cancer 

The National Cancer Institute, as leader of the National Cancer Program, provides vision and direction to the national 

community of researchers, public health workers, healthcare providers, patients, advocates, and policymakers working 

to defeat cancer. Our success will be measured by our ability to leverage resources, remove the major barriers that 

impede progress, and ensure that all new activities reflect past lessons learned. We must maintain our momentum so that 

the progress we have made leads us into a better future for those with, or at risk for, cancer. We will reach our Challenge 

Goal through investments in scientific research, technology leadership and capacity building, application in public health 

and patient care, and communication and transfer of results. 

Scientific Research 

NCI supports a broad range of scientific research 

to expand our understanding of cancer at the 

molecular level and to learn how its development 

and progression are affected by behavioral and 

environmental factors. These insights provide the 

foundation for new interventions and strategies 

in prevention, control, early detection and diagnosis, treatment, and follow-up care. 

Each year, NCI supports nearly 5,000 principal investigators to perform research projects 

that result in better ways to combat cancer. 

These dedicated scientists conduct studies at 

NCI (intramural) and at nearly 650 universities, 

hospitals, and other sites in almost every State 

in the Nation and in more than 20 foreign 

countries. Intramural research activities serve 

as hubs for new development through cutting 

edge basic, clinical, and epidemiological research. 

Extramural program experts provide guidance 

and oversight for research conducted at universities, teaching hospitals, and other organizations. 

Technology Leadership and Capacity Building 

NCI leads the Nation in using innovative 

approaches for harnessing the full potential 

of advanced technologies for cancer. Recent 

advances in bioinformatics are dramatically 

accelerating the rate with which we can process 

large amounts of information. New molecular 

imaging and biosensing technologies are opening 

doors to faster, more accurate detection and 

diagnosis, facilitating more precise imageguided therapies, and making it easier to monitor 

treatment outcomes. Nanomedicine offers hope 

for streamlining cancer care through revolutionary preventive, diagnostic, and therapeutic 

applications. 

We help to build the capacity of the cancer 

research enterprise through NCI-supported 

centers, networks, and consortia that allow 

scientists from around the world to share their 

expertise and resources. NCI provides incentives 

for research in special areas of need and for 

collaborative efforts that promote interdisciplinary team science. Tissue samples, statistics on 

cancer incidence and mortality, databases of 

genetic information, imaging databases, mouse 

models of cancer, full length gene clones, and 

software for analyzing statistical and genetic 

data are provided to investigators in all research 

settings at little or no cost.
THE NATIONAL CANCER INSTITUTE 3 

Our new paradigm for eliminating the suffering and death due to cancer is to preempt its initiation and progression at every 

possible point. We must prevent cancer initiation whenever possible, eliminate it in its early stages when it does occur, and 

help cancer patients live with, rather than die from, the disease. NCI supports basic research and intervention development 

and works with others to incorporate evidence-based prevention strategies into public health programs and medical practice. 

New molecular diagnostics are on the horizon that will help us make earlier and more individualized assessments and improve 

the potential for the successful elimination of some cancers. And more targeted therapies and new delivery technologies promise 

to dramatically improve our ability to control or modulate the effects of other cancers. 

Application in Public Health and Patient Care 

NCI is working with other agencies and organizations to bridge the gap between the promise 

of research and its application for people. We 

work to ensure that newly developed interventions move through well designed, well run 

clinical trials and that those found effective and 

safe are made available to cancer patients 

everywhere. Institute leaders have established 

partnerships with the Food and Drug Administration and the Centers for Medicare and 

Medicaid Services to speed the development 

of and improve access to safe and affordable 

cancer prevention, early detection, and treatment options. Others work with Federal, State, 

and local agencies and other organizations to 

develop and support the use of evidence-based 

tobacco control strategies and promote healthier 

diets and exercise programs known to be preventive against a number of cancers. In addition, 

several Patient Navigator Programs are being 

piloted around the country and will be evaluated for their efficacy and cost effectiveness in 

helping cancer patients gain access to cancer 

prevention information, screening, diagnosis, 

treatment, and follow-up care. NCI is also 

playing a leadership role in Health and Human 

Services Department-wide efforts to eliminate 

health disparities in our country

Communication and Transfer of Results 

NCI provides Web-based information on cancer 

and clinical trials, toll-free telephone service in 

all regions of the country, and printed 

brochures and educational packages distributed 

directly to cancer patients and their families as 

well as to oncology practices and patient advocacy organizations. The NCI Cancer Research 

Portfolio and the International Cancer Research 

Portfolio Web sites provide invaluable resources 

to investigators desiring to locate research information or find collaborators in areas of interest. 

We foster collaborations for the transfer of 

research results through liaisons with other 

organizations. For example, NCI’s Cancer 

Information Service Partnership Program focuses 

on reaching minority and other medically underserved populations. Partnering with over 450 

public and private organizations nationwide, we 

collaborate on data driven, outcome oriented 

education and public health projects and provide 

technical assistance to build capacity in clinical 

trials, breast and cervical cancer screening, general cancer awareness, and tobacco education. 

.
Our Strategic 

Investments 

for Fiscal 

Year 2006 

Molecular Epidemiology 

PAGE 48 

Understand the behavioral, genetic, and 

epigenetic causes of cancer and use this 

knowledge to generate new means of 

preventing, detecting, and treating cancers. 

■ Investigate specific types of cancer through 

cohort, case-control, and family-based 

consortial studies. 

■ Research behavioral and environmental 

risk factors. 

■ Integrate population science with genomics 

and other technologies. 

■ Build partnerships and interdisciplinary 

research. 

Integrative Cancer Biology 

PAGE 42 

Understand the complex networks within 

cancer cells and between cancer cells and 

their environment to discover new leads 

for cancer prevention, detection, diagnosis, 

and treatment. 

■ Develop computational models of 

biological systems. 

■ Support studies of the tumor 

microenvironment. 

■ Conduct tumor macroenvironment 

research. 

Advanced Technologies 

PAGE 32 

Accelerate the development and use of 

advanced technologies to enhance patient care 

and connect investigators with one another 

and with healthcare providers and patients. 

■ Build bioinformatics infrastructure and 

tools. 

■ Develop and apply advanced imaging 

technologies to cancer research and care. 

■ Support proteomic technology development 

for overcoming barriers to early detection. 

■ Continue to foster the use of nanotechnology 

for cancer research and care. 

See also: 

When We Reach Our Challenge Goal 

INSIDE FRONT COVER 

Building Research Teams of the Future 

PAGE 26 

National Advanced Technologies Initiative 

for Cancer 

PAGE 40 
Cancer Prevention, Early Detection, 

and Prediction 

PAGE 6 

Develop new medical approaches and 

evidence-based public health interventions 

and policies to substantially reduce the 

incidence of and improve prognosis for 

cancer. 

■ Support development of new technologies and approaches to prevention, 

through tobacco control, energy 

balance, vaccines, and new drugs. 

■ Develop biomarkers and imaging 

techniques for early detection. 

■ Develop predictors of cancer risk and 

treatment success. 

Overcoming Cancer Health Disparities 

PAGE 14 

Discover the causes of health disparities, 

develop interventions to reduce them, 

and facilitate intervention delivery. 

■ Conduct community-based, 

multidisciplinary, collaborative 

studies to understand the causes of 

health disparities. 

■ Develop culturally appropriate interventions 

and assess their efficacy. 

■ Establish collaborations for research, 

translation, and application. 

■ Train minorities in health care and 

research. 

An Integrated Clinical Trials System 

PAGE 28 

Build a highly interactive and optimally 

coordinated cancer clinical trials system that 

will prioritize and accelerate the development 

of new, effective interventions and ensure that 

they are incorporated into medical practice. 

■ Strengthen scientific prioritization and 

coordination. 

■ Speed novel agent development and marker 

validation. 

■ Expand the goals of clinical trials to 

include health disparities research, 

symptom management, quality of life, 

and other areas of focus. 

Strategic Development of Cancer 

Interventions 

PAGE 20 

Optimize the transfer, development, and 

delivery of highly effective molecularly targeted 

drugs and technologies to specifically prevent, 

detect, diagnose, and treat cancer. 

■ Expand existing programs to increase the 

number of new drug candidates and new 

interventions for understudied malignancies. 

■ Invest in enterprise initiatives for biospecimen 

resources and large-scale genome analysis. 

■ Build capacity for biomarker discovery 

and development and target validation. 

■ Support program integration and new 

technologies for preclinical development. 

Delivering the Promise 

NCI’s Budget Increase Request Emphasizes 

Patient Care and Public Health 

PAGE 52 

Fiscal Year 2006 Budget Request 

PAGE 54 
6 THE NATIONAL CANCER INSTITUTE 

Strategic Investments in Cancer Prevention, Early Detection, and Prediction 

Our Goal Substantially reduce the incidence of cancer and integrate early detection 

with markers of prognosis, through the development and effective delivery of medical 

approaches to prevention and early detection and the promotion of effective, evidencebased public health interventions and policies. 

Newly aligned goals focused on preventing cancer from occurring and detecting it early when 

it is most curable are at the heart of our Nation’s research and public health agendas. Dramatic 

developments in technology and a more complete understanding of the causes and mechanisms 

of cancer will enable us to provide more effective ways to prevent the disease. New evidencebased interventions encourage lifestyle improvements in diet and physical activity, discourage 

smoking, and promote the use of safe and fully tested chemoprevention approaches for people 

at risk. Pioneering proteomic and biomarker advances and the promise of nanotechnology give 

us new hope for the early detection and diagnosis of cancer and prediction of patient response 

to treatment. Advanced information systems and methods of evaluation will maximize the impact 

of existing technologies. We are ramping up specimen repositories and widely accessible 

bioinformatics resources to support the development of these breakthroughs. 

Prevention is our first line of defense against cancer. 

The prevention of cancer focuses on studying and modifying behaviors that increase risk, 

mitigating the influence of genetic and environmental risk factors, and interrupting the 

carcinogenesis process through early medical intervention. We can save many lives, for example, 

by continuing to advance understanding of the biological and behavioral basis of nicotine 

addiction and energy balance. The 2004 Surgeon General’s Report, The Health Consequences 

of Smoking,

1 estimates that smoking causes 159,600 cancer deaths each year including cancers 

of the lung, mouth, stomach, bladder, pancreas, esophagus, and larynx. New medications to 

help smokers quit are under development and current evidence suggests that information 

and referrals from quit lines, as well as behavioral counseling from healthcare providers, 

significantly increase abstinence rates. Current evidence also suggests that increasing the price 

of cigarettes and establishing tobacco-free work places and public areas significantly decrease 

smoking prevalence. 

State and community programs and policies play a critical role in the prevention and control 

of tobacco use. Because State and local funds have been severely limited in recent years, it is 

especially important to understand the differential impact of various activities. For example, 

better insights are needed on how best to implement evidence-based interventions, how to 

effectively combine clinical- and population-based smoking cessation efforts, and the impact 

of more widespread clean indoor air laws on smoking prevention and cessation. 
THE NATIONAL CANCER INSTITUTE 7 

Tobacco use and tobacco-related cancers are also a large and increasing threat to health in the 

developing world. The International Agency for Research on Cancer (IARC), part of the World 

Health Organization,2 coordinates and conducts both epidemiological and laboratory research 

into the causes of cancer, including tobacco use. As resources permit, NCI will provide funds 

for IARC research and dissemination efforts. With additional resources for tobacco control in 

Fiscal Year 2006, we will: 

■ Fund research to increase our knowledge of effective State and community program and policy 

interventions for tobacco control and prevention. 

■ Support IARC tobacco control and prevention research and dissemination activities to benefit 

low- and middle-income nations. 

■ Fund multidisciplinary research on the interplay of behavior, chemistry, toxicology, and biology 

to determine the cancer risk potential of reduced-exposure tobacco products. 

Stop Smoking Programs Are Pivotal for Preventing Several Types of Cancer 

Tobacco use remains the single most preventable cause of death in the United 

States, accounting for approximately 440,000 deaths in the United States each year. 

About 46 million people in our country, or 23 percent of the population, currently 

smoke. Cigarette smoking contributes to nearly one-third of all cancer deaths. Tobacco 

use is a major risk factor for lung cancer as well as cancers of the esophagus, larynx, 

kidney, and pancreas. 

The health benefits of smoking cessation are immediate and substantial. Within just 

a few days of quitting, a person’s sense of taste and smell return, breathing becomes 

easier, and blood pressure returns to normal. After 15 to 20 years, a previous tobacco 

user’s risk of premature death approaches that of a person who has never smoked. 

About 10 years after quitting, an ex-smoker’s risk of dying from lung cancer is 30 to 50 percent less than 

the risk for those who continue to smoke. Research suggests that people who stop smoking before the 

age of 35 reduce their risk of developing a tobacco-related disease by 90 percent. 

The American Stop Smoking Intervention Study (ASSIST),1 funded by NCI, provides the latest evidence 

that investing in State tobacco control programs can reduce smoking rates. The goal of ASSIST is to 

change the social, cultural, economic, and environmental factors that promote smoking by utilizing four 

policy strategies: promoting smoke-free environments; countering tobacco advertising and promotion; 

limiting youth access to tobacco products; and raising excise taxes to increase the price of tobacco products. 

The interventions have been developed and implemented by networks of state and local tobacco control 

coalitions. ASSIST was evaluated by comparing data regarding changes in adult smoking prevalence, per 

capita cigarette consumption, and tobacco control policies between the 17 ASSIST states and the 33 

non-ASSIST states and the District of Columbia. NCI estimates that if all 50 states and the District of 

Columbia had implemented ASSIST, approximately 1,213,000 fewer people would smoke. 

1 cancer.gov/newscenter/pressreleases/ASSISTQandA
8 THE NATIONAL CANCER INSTITUTE 

Inadequate nutrition and physical activity appear to contribute to a sizable proportion of cancers. 

A comprehensive review by IARC, conducted in 2002, summarized compelling evidence that 

prevention of obesity reduces risk for a number of common cancers and that physical activity 

reduces risk for colon and breast cancers. There are still questions, however, about the specific 

causative and protective components in a person’s diet as well as the carcinogenic mechanisms 

associated with an overweight and sedentary lifestyle. With additional resources for energy balance 

research in Fiscal Year 2006, we will: 

■ Expand research at centers for Transdisciplinary Research on Energetics and Cancer (TREC) 

to enhance our understanding of the mechanisms underlying the association among energetics, 

energy balance, and cancer and to develop effective innovative approaches for prevention 

of obesity. 

■ Conduct studies to identify the molecular mechanisms of bioactive food components as modifiers 

of cancer risk and tumor behavior. 

■ Explore the utility of nanotechnologies related to proteomics and metabolomics to evaluate 

physiological changes influenced by dietary components in normal and cancerous processes. 

■ Work with bioengineers to develop new technologies for assessing energy intake and balance. 

NCI is supporting the development of prevention vaccines and drugs for suppressing the 

carcinogenic process either at its inception or in pre-invasive stages. A new vaccine that targets 

the infectious agent human papilloma virus (HPV), implicated in cervical cancer, is being 

tested in clinical trials and is anticipated to be available to women at risk in the near term. 

Through the use of medicines, vitamins, food compounds, and other substances, we can halt 

or reverse the progression of disease in people with precancerous conditions and in people 

at risk for cancer. Preclinical studies will identify prevention agents that impact cellular level 

targets to intervene in the cancer process, and clinical trials will test the value of these agents 

in preventing disease. With increased resources in Fiscal Year 2006, we will: 

■ Promote studies that evaluate second generation HPV vaccines that could most easily be 

adopted in public health strategies in the United States and elsewhere and that could both 

protect against initial infection and promote its eradication among those already infected with 

the family of viruses that causes cervical cancer. 

■ Conduct preclinical and Phase I and II clinical studies to identify cellular targets and screen 

potential agents for the prevention of hormonally non-responsive breast cancer and cancers 

in former smokers. 

■ Accelerate the discovery and development of agents to help smokers quit and prevent cancers 

in former smokers. 

■ Complete Phase II trials for three chemopreventive agents and begin Phase II trials for another 

three agents each for breast, prostate, colorectal, and lung cancers. 
THE NATIONAL CANCER INSTITUTE 9 

As we make such breakthroughs, we must actively translate prevention research into improved 

outcomes and facilitate the role of public policy to see that all people have knowledge of and access 

to preventive medicine and approaches. We will use additional resources in Fiscal Year 2006 to: 

■ Increase adoption of evidence-based prevention approaches in primary care and public 

health service sectors through existing partnerships with the Centers for Disease Control and 

Prevention (CDC) and national advocacy organizations. 

■ Monitor the incorporation of evidence-based preventive interventions into the delivery of 

clinical care, through provider surveys and partnerships with HMO networks. 

■ Develop effective strategies for communicating risk prediction and perception to health 

professionals and patients. Inform these strategies by evaluating public comprehension of 

health recommendations through the NCI Health Information National Trends Survey3 and 

by collaborating with other HHS agencies to conduct periodic surveys of healthcare providers 

to evaluate cancer-related knowledge, attitudes, and practices. 

Energy Balance Plays a Major Role in Cancer Prevention and Control 

Energy balance is a term used to describe the complex interplay of physical activity, diet, 

genetics, and body size and its impact on health. Physical inactivity, overweight and obesity 

increase the risk of numerous cancers including cancers of the breast, colon, endometrium, 

and kidney. However, the precise mechanisms by which energy balance influences cancer risk 

are not yet fully understood. NCI, in collaboration with partners throughout NIH, is conducting 

and funding cutting-edge research to elucidate these mechanisms and better understand how 

people can modify the risk factors that lead to overweight and obesity. 

NCI’s investigation of the relationship between energy balance and cancer includes active 

participation in the NIH Obesity Research Task Force,1 which recently issued recommendations 

and goals for research on obesity and how it impacts health outcomes. In line with the task 

force’s goals, we have embarked on several collaborations. One is with the National Institute of 

Environmental Health Sciences to fund research on how the “built environment” – i.e., how 

buildings are structured, open spaces are utilized, and people view and use their surroundings – affects diet, 

physical activity, and weight control practices. A collaboration with the National Heart, Lung, and Blood 

Institute focuses on a bioengineering initiative to develop objective measures relevant to energy balance. We 

have also launched a new cutting-edge initiative to establish centers for Transdisciplinary Research on 

Energetics and Cancer to form transdisciplinary teams of scientists to accelerate progress in reducing 

cancer incidence, morbidity, and mortality associated with obesity, low levels of physical activity, and poor 

diet. NCI supports innovative research on economic factors impacting energy balance, and the relationship 

between energy balance and cancer using pre-existing biological specimens from ongoing case control or 

cohort studies. Finally, we continue to support research on improving the assessment of diet and physical 

activity, ranging from studies of biological measures of energy intake and expenditure to a conference on the 

use of e-technologies to assess and modify physical activity, diet, and energy balance in real time. 

1 obesityresearch.nih.gov/about/about.htm#taskforce
10 THE NATIONAL CANCER INSTITUTE 

Early detection can eliminate a large proportion of deaths due to cancer. 

Detecting cancer before metastasis begins can dramatically improve the odds of survival. 

For example, evidence suggests that 90 percent or more of colorectal cancer deaths could be 

prevented if precancerous polyps were detected with routine screening and removed at an early 

stage. Yet, the screening rate for colorectal cancer lags far behind that of other cancers, and the 

disease remains the second leading cause of cancer death in our Nation. This situation will be 

reversed only when we develop less invasive screening techniques and overcome psychosocial 

barriers to screening and follow-up therapy. For still other cancers – e.g., ovarian and pancreatic 

– there are no reliable early-stage screening tests to offer patients. For others, such as prostate

cancer, screening tests are available but have not been proven to reduce mortality. NCI’s Early 

Detection Research Network (EDRN)4 and the NCI/FDA Clinical Proteomics Program5 are 

developing non-invasive screening and early detection tests for early stage ovarian, prostate, and 

other cancers. We will use increased resources for early detection in Fiscal Year 2006 to: 

■ Expand the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial6 

biorepository to include collection of tissues from diagnosed cancer patients. 

■ Build a National Lung Screening Trial Image Library to develop and optimize the use of 

computer-aided diagnostic programs for early detection of lung cancer and use images to 

develop a risk stratification algorithm. 

■ Develop screening approaches that use a combination of body fluid biomarkers and imaging 

technologies for detection of breast, lung, colorectal, cervical, oral, gastrointestinal, genitourinary, and reproductive cancers. 

■ Support molecular imaging approaches for the early detection of precancerous lesions. 

■ Develop minimally invasive treatments for screen-detected tumors. 

Research Network Advances Prevention and Early Detection 

The Early Detection Research Network (EDRN) promotes collaboration among researchers by creating an 

environment of cross-fertilization and teamwork among different disciplines and laboratories to achieve 

common goals. It is comprised of a group of 28 NCI grantees focused on creating validated biomarkers, 

including those with the potential to be surrogate endpoints for clinical trials, ready for large-scale clinical 

testing. EDRN is at the forefront of technology-driven research on the early detection of cancer and 

carcinogenesis and a leader in the disciplined establishment and use of criteria for the validation of markers 

of risk and precancerous changes. Current validation studies include microsatellite analysis, a promising 

molecular diagnostic technology for diagnosis of kidney cancer and protein expression profiling of body 

fluids, a novel approach for the early detection of prostate cancer. The Network is also a leader in the creative 

use of information technology and the sharing of data. EDRN has pioneered the development of common 

data elements to speed consistency in data description across institutions and has implemented informatics 

solutions to enable data sharing among laboratories. 
T H E N A T I O N A L C A N C E R I N S T I T U T E 11 

■ Evaluate the quality-of-life benefits of prevention and screening. 

■ Create national standards for performance measures and work with public and private 

organizations to collect and analyze data for monitoring the success of screening and early 

detection programs. 

Prediction of risk and outcomes optimizes individualized cancer interventions. 

More accurate methods for predicting who is at high risk for developing cancer and which 

treatment option(s) would be most effective on a patient-by-patient basis will contribute 

significantly to reducing the cancer burden. We know that individual susceptibility based on 

clinical, epidemiologic, genetic, and biological factors can influence the outcome of a given 

prevention or treatment strategy. NCI’s EDRN develops, evaluates, and validates biomarkers 

that will be used for prediction of individualized cancer risk and treatment success. High 

throughput genomic and proteomic prediction techniques are being developed to help guide 

treatment choice for individual patients with leukemia, lymphoma, and other cancers. With 

additional support for prediction studies in Fiscal Year 2006, we will: 

■ Develop risk prediction models for individual cancer risk and success of treatment, incorporating clinical, epidemiologic, genetic, and biologic factors. Develop assays to discover and validate 

risk and treatment markers for precancers and cancers to inform these risk models. Create 

annotated specimen repositories to test and compare markers. Develop strategies to swiftly 

move markers and risk prediction models from discovery through development and into delivery. 

■ Use NCI’s Cancer Intervention and Surveillance Modeling Network (CISNET)7 to 

synthesize knowledge about existing and 

emerging cancer risk factors, prevention and 

early detection strategies, current levels of 

usage, and anticipated future dissemination 

to project their impact on population trends 

in cancer incidence and mortality. 

■ Accelerate the identification of markers of 

cancer risk and cancer progression in high risk 

populations. 

■ Evaluate new and emerging endoscopic 

imaging technologies for risk and chemopreventive response in Phase I and II intervention trials. 

1 surgeongeneral.gov/library/smokingconsequences 

2 www.iarc.fr 

3 cancercontrol.cancer.gov/hints 

4 cancer.gov/prevention/cbrg/edrn 

5 cancer.gov/newscenter/proteomicsFDA 

6 cancer.gov/prevention/plco/index.html 

7 cisnet.cancer.gov/index.html 

Cancer Prevention, Early Detection, and Prediction 

Budget Increase Request for Fiscal Year 2006 

Strengthening cancer prevention $75.00 M 

Tobacco control 

Energy balance research 

Prevention vaccines & drugs 

Translation of research into improved outcomes 

& public policy 

Developing & improving early detection options 16.50 M 

Biospecimen repositories 

Lung screening image library 

Biomarkers & molecular imaging for pre-cancerous lesions 

Evaluation and monitoring 

Predicting cancer risk & treatment success 18.75 M 

Risk prediction markers & models 

Intervention & surveillance modeling 

Markers of risk in high risk populations 

Endoscopic imaging 

Management & Support 1.87 M 

Total $112.12 M
12 THE NATIONAL CANCER INSTITUTE 

The most efficient way to prevent death from cancer is to focus on stopping people from getting it in the 

first place. NCI is researching promising prevention strategies that use prevention agents and vaccines 

both separately and in combination. Three examples follow. 

Preventing Prostate Cancer with Prevention Agents 

Improvements in early detection and treatment have contributed to more than a decade-long decline in 

prostate cancer mortality. Still, about one-fourth of treated patients ultimately die of their disease – and 

even at the earliest stages of prostate cancer, treatment can cause significant side effects. Investigators 

are searching on several fronts for effective chemoprevention agents for prostate cancer. 

The Prostate Cancer Prevention Trial (PCPT)

New Prevention Strategies Hold Promise for Halting Cancer Before It Develops 

1 was designed to test the drug finasteride (PROSCARTM), which 

is used to treat benign enlargement of the prostate, as a possible preventive for cancer in men aged 55 

and older. In July 2003, PCPT researchers presented findings demonstrating that prostate cancer can be 

prevented, at least in part, by this intervention. Men in the study who took finasteride for seven 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. The investigators have developed an ambitious program of laboratory 

studies to look at the molecular biology of prostate cancer using blood and tissue samples collected 

during this landmark clinical trial. These studies will help clarify who is at greater risk for developing this 

disease and who might benefit most from finasteride therapy. 

Other agents under study include anti-androgens and anti-estrogen drugs, 

micronutrients, and anti-inflammatories. The Selenium and Vitamin E Cancer 

Prevention Trial (SELECT),2 which will test the impact of these supplements on 

prostate cancer risk, has completed recruitment of more than 35,000 men and 

includes a biorepository to address molecular level research questions. 

Preventing Cervical Cancer through Vaccination 

Successful interventions in early detection have helped to reduce deaths due to 

cervical cancer, especially in developed countries such as the United States. 

However, not all women have ready access to screening tests, and cervical 

cancer remains the most common cause of cancer death among women 

worldwide. Estimates suggest that 3,900 women in the United States will die 

from cervical cancer this year. If healthcare communities around the world 

had a simple means of preventing cervical cancer, hundreds of thousands of 

lives could be saved every year. NCI and partners are pursuing a vaccination 

strategy to do just that. Scientists are designing vaccines to prevent cervical 

cancer by protecting women against persistent infection with the human 

papilloma virus (HPV), the cause of virtually all cases of cervical cancer.
THE NATIONAL CANCER INSTITUTE 13 

Through years of preclinical development and early clinical testing, researchers have designed a vaccine 

composed of virus-like particles that are produced through recombinant DNA technology. Vaccination 

causes the immune system to recognize and attack not just the virus-like particles, but also the true HPV 

virus, which the particles resemble. Two large pharmaceutical companies, Merck and GlaxoSmithKline 

(GSK), have licensed the vaccine technology from NIH and are developing versions that target the most 

common cancer-causing strains of HPV. In early clinical trials, these vaccines have conferred 100 percent 

protection, in fully vaccinated women, against persistent infection by the HPV type(s) targeted. Both 

companies have begun large, international Phase III clinical trials, a landmark step in development. NCI, 

together with public health researchers, are conducting a parallel efficacy trial of the GSK vaccine in Costa 

Rica, where cervical cancer is the most common female tumor. 

Combining Prevention Drugs and Vaccine Strategies to Prevent Colorectal Cancer 

Researchers are exploring strategies that combine the use of chemoprevention agents with vaccines. One 

team of NCI researchers recently used a mouse model to study human familial adenomatous polyposis 

(FAP). This disease genetically predisposes affected individuals to develop numerous colon polyps, 

followed by early onset colorectal cancer. The mice in this study were designed to develop tumors that 

mirror the pathology of FAP. There were three treated groups of mice. One was fed a diet containing the 

drug celecoxib (Celebrex®), which is used to reduce FAP polyp formation in people. A second group was 

given the experimental CEA3 vaccine, designed to prevent colorectal tumors. The third group was given 

both celecoxib and the vaccine. Although mice in all three groups developed fewer tumors than untreated 

mice, the group that was both fed celecoxib and vaccinated did the best, with 95 percent less tumor 

development and significantly improved overall long-term survival compared to the untreated group. 

This groundbreaking research removed considerable doubt about the feasibility of effectively combining a 

potent anti-inflammatory agent like celecoxib with vaccination. Because tissue inflammation is an immune 

response, usually to injury or infection, it seemed clear that celecoxib must act by at least partially 

suppressing the immune system. On the other hand, vaccines work by stimulating the immune system 

to attack tumor cells. Because of the opposing nature of their activity, many suspected that celecoxib and 

vaccination would need to be used separately. The present study has shown that, despite having some 

effect on the immune system, celecoxib indeed could work synergistically with vaccination. Clinical trials 

have shown the safety of the CEA vaccine in colorectal cancer patients. The next step will be to establish 

the long-term safety of the CEA vaccine in people. 

1 cancer.gov/pcpt 

2 cancer.gov/clinicaltrials/digestpage/SELECT 

3 carcinoembryonic antigen 
14 THE NATIONAL CANCER INSTITUTE 

Strategic Investments for Overcoming Cancer Health Disparities 

Our Goal Overcome the unequal burden of cancer experienced by various population 

groups by discovering the fundamental causes of cancer health disparities, developing 

effective interventions to reduce those disparities, and facilitating intervention delivery. 

Some of our greatest opportunities for reducing the burden of cancer reside with our efforts to 

overcome cancer health disparities. Research studies have provided definitive evidence that 

equal treatment at the same stage of disease yields equal outcomes across all populations. By 

providing universal access to the currently tested and available interventions for the prevention, 

early detection, and treatment with follow-up for breast, cervical, and colorectal cancers, we 

could see a dramatic reduction in cancer mortality. Similar improvements would occur for 

other types of cancer within minority and medically underserved populations with consistently 

applied interventions for tobacco control and energy balance and equal access to clinical trials 

and state-of-the-art cancer care. 

As emphasized by the Trans-HHS Cancer Health Disparities Progress Review Group1 in their 

March 2004 report, collaborations among Federal, State, and local decision makers are needed 

to facilitate the development and adoption of policies to eliminate health care access barriers 

and to promote quality health education and prevention strategies that lower the risk of cancer. 

We know that disparities occur at the local level and that the reduction of these disparities 

depends on community participation. NCI has established the Community Networks Program2 

to focus on developing strategies to help communities achieve these objectives. Communities, 

caregivers, and researchers must form strong alliances and explore creative solutions for 

developing culturally competent venues for service delivery. Community-based participation 

must be an integral part of the planning, development, and implementation of solutions to 

bring research advances to all populations. This cross fertilization will build synergism and 

ensure stronger, more dynamic alliances for overcoming cancer health disparities. 

Determining the Underlying Causes and Extent of Cancer Health Disparities 

One of our objectives at NCI is to support research to better understand and address the causes 

of cancer health disparities. Studies in epidemiology and the biology of aging aid in the identification and characterization of the causes of cancer among various population groups. (See 

pages 44 and 48-49.) Linking this knowledge to the effects of poverty, culture, and social injustice is a critical next step to gain a full understanding of and be able to adequately address cancer health disparities. While health disparities have historically been framed in terms of racial 

and ethnic categories, recent research has dispelled the biological basis of racial categories. 

Scientists have provided strong evidence that racial classification is a social and political rather 

than a biological construct. However, these classifications may act as indicators or surrogates 

for social injustice, particularly as they relate to factors such as low economic status, cultural 

generalizations, and perceived genetic similarities. With sufficient resources for these studies in 

Fiscal Year 2006, we will: 

■	 Continue to examine relationships between genetics and race or ethnicity in order to inform 

the proper use of these variables in research, through a partnership with the National Human 

Genome Research Institute. 
THE NATIONAL CANCER INSTITUTE 15 

■ Conduct think tanks to synthesize the anthropological, historical, social, biological, and 

medical literature regarding race, ethnicity, and genetics and expand our understanding of how 

health disparities develop. These think tanks will be conducted collaboratively with experts 

from the extramural community and the National Human Genome Research Institute. 

■ Conduct multidisciplinary intervention studies on disparities and the economics of cancer, 

access to cancer treatment and prevention trials, and other cancer control issues such as diet 

and physical activity, in collaboration with the NIH Office of Behavioral and Social Sciences 

Research and the Agency for Healthcare Research and Quality. 

■ Expand epidemiologic studies exploring racial and ethnic cancer disparities and establish 

new approaches for data collection and sharing to ensure cross-cultural equivalence and the 

use of variables such as race, ethnicity, and socioeconomic status in the study of cancer. 

Charting the Course for Overcoming Cancer Health Disparities 

Cancer health disparities occur within the broad context of human 

circumstances, including substandard housing, poor educational 

opportunities, adverse environmental exposures, and limited access 

to quality health care. Viewing health disparities through the historic and present-day lens of inequity and 

social injustice reveals a complex problem. 

Overcoming cancer health disparities is more than a priority goal of the NCI. It is the will of the Nation. In 

2002, the President of the United States and the Department of Health and Human Services charged a 

group of experts with reviewing the status of health disparities and charting a course toward closing the 

gap using cancer as the model. In its landmark report, Making Cancer Health Disparities History, 

1 the 

Trans-HHS Cancer Health Disparities Progress Review Group (CHD PRG) enthusiastically endorsed a 

"Call to Action" consisting of an integrated set of forward thinking recommendations to be implemented 

by the Department and its agencies. 

Several of the CHD PRG recommendations are addressed in NCI's planned investments for Fiscal Year 

2006. "New approaches for data collection and sharing," as recommended by the PRG, will be developed 

via NCI-supported epidemiologic studies to ensure cross-cultural equivalence and the appropriate use of 

variables such as race, ethnicity, and socioeconomic status in the study of cancer. Community Networks 

to Reduce Cancer Health Disparities will "support the development of sustainable community-based networks for participatory research." The Tobacco and Health Disparities Research Network will research, 

develop, and "implement evidence-based tobacco control strategies" on a large scale. Training programs 

co-sponsored by minority institutions and the Community Networks to Reduce Cancer Health Disparities 

will support the creation of a "diverse and culturally competent cancer care workforce." 

The Progress Review Group has charted a course for overcoming cancer health disparities throughout our 

Nation. With sustained resources and careful planning, NCI will continue to lead the way toward achieving 

this goal to make cancer health disparities history. 

1 www.hhs.gov/chdprg
Preventable Cancer Incidence and Mortality Plague Specific Population Groups 

Dr. Harold P. Freeman, 

Director of the NCI 

Center to Reduce Cancer 

Health Disparities, is 

leading an effort to 

publicize "A Lion in the 

House," a documentary 

to be aired on PBS in 

2006. The series will 

follow five families whose 

experiences across six 

years of fighting cancer 

reveal issues related to 

health disparities and 

the unequal burden of 

disease in American 

society. 

Distinguished by race/ethnicity, gender, age, socioeconomic status, geographic location, 

occupation, and education, underserved population groups across the United States suffer 

disproportionately high cancer incidence and mortality rates for a variety of reasons. These 

individuals are significantly more likely than the overall U. S. population to: 

■ Be diagnosed with and die from preventable cancers. 

■ Be diagnosed with late stage disease for cancers detectable at an early stage through 

screening. 

■ Receive either no treatment or treatment that does not meet currently accepted standards 

of care. 

■ Die of cancers that are generally curable. 

■ Suffer from terminal cancers in the absence of adequate pain control and other palliative care. 

Across all racial and ethnic groups, the five-year survival rate is more than 10 percent higher for affluent 

populations than for persons who live in poorer areas. Screening for colorectal, female breast, cervical, and 

prostate cancers is widely recommended and practiced. Yet, in high poverty areas, the proportion of cancers 

diagnosed in early, more treatable stages versus those at more advanced, less treatable stages is lower 

than in low poverty areas. For example, white men in Kentucky, a largely rural state with high poverty levels, 

are more likely to die from cancer than white men in any other U.S. state. A recent comprehensive review 

of treatment response for people in poorer economic groups documented substantial differences in receipt 

of optimal treatment, including definitive primary therapy, adjuvant therapy, conservative surgery, and 

follow-up after potentially curative treatment. 

Recent information on cancer incidence and death rates may reflect socioeconomic characteristics of large 

populations within racial and ethnic minority groups. African Americans have the highest death rate from 

all types of cancers combined and from malignancies of the lung and bronchus, colon and rectum, female 

breast, prostate, and uterine cervix of all racial or ethnic groups in the United States. Vietnamese women 

experience invasive cervical cancer, largely preventable by screening, at a rate four times as high as all 

Asian American and Pacific Islander populations combined. Some Asian populations have nasopharyngeal 

and stomach cancer rates that are unusually high. And Hispanics have had incidence rates of liver and 

intrahepatic bile duct cancer that were more than 50 percent higher than in the overall population. 

Close to 60 percent of all new cancers and 70 percent of deaths from cancer are in persons older than 65, 

another underserved population. The economic burden of cancer is also taking its toll. As our Nation’s 

population ages, more people will get cancer. Meanwhile, the costs of cancer diagnosis and treatment are 

on the rise. The combination of these trends will accelerate a rise in the costs of cancer treatment and 

exacerbate the impact of cancer on people with limited resources. 

Individuals affected by cancer bear other burdens as well. Those who have cancer or who must care for 

someone with cancer are often unable to maintain employment or devote time to other family members. 

Cancer is clearly much more than a medical problem. It is a serious socioeconomic dilemma. 

16 THE NATIONAL CANCER INSTITUTE
THE NATIONAL CANCER INSTITUTE 17 

■ Fund and conduct basic, clinical, and epidemiologic studies jointly designed with 

community groups, including the Community Networks Program and existing Federal clinics 

and pilot programs to understand reasons for disparities in cancer risk, including racial/ethnic, 

socioeconomic, cultural, environmental, and geographic factors. 

■ Foster community studies on individual behaviors and environmental factors to advance 

knowledge about specific local populations. 

■ Translate national health survey questions so that they can be administered among speakers 

of Spanish, Chinese, Vietnamese, Korean, and other languages. 

■ Continue support for the newly created Cancer Council of the Pacific Islands, a communitybased team comprised of health care leaders who can articulate the cancer health needs of 

indigenous people in each of the six U.S. associated jurisdictions of the Pacific Rim. 

■ Establish a Federal Task Force with representatives from the Cancer Council of the Pacific 

Islands, NCI, NIH, and other Federal agencies with programs and resources dedicated to the 

Pacific Rim, to collaborate in strengthening and sustaining community capacity for addressing 

cancer health disparities. 

Evaluating Promising New Interventions 

Our investments in new strategies for cancer interventions must be tested and applied across 

various populations in a culturally appropriate and community-specific manner. To do this, we 

first need to draw on science-based knowledge about the causes and variables contributing to 

health disparities while developing interventions. Once developed, it is critical to assess the efficacy of these interventions across all relevant population groups in terms of reduced prevalence 

of risk factors, incidence, and mortality and improved survival and quality of life. With additional resources in Fiscal Year 2006, we will: 

■ Support innovative scientific research to assess risk and other aspects of behaviors associated 

with the specific sociocultural environments of cancer patient populations and develop 

interventions tailored to cultural and geographic influences. 

■ Support tobacco use prevention and cessation research and intervention development for 

underserved and understudied youth and young adults. 

■ Support observational and intervention research that focuses on cancer survivorship in 

medically underserved, low income, ethnic, and minority populations. This research will 

cover access to and quality of care; the incidence of side effects and management of long-term 

health; quality of life; health behaviors such as diet, exercise, and tobacco use; and the 

socioeconomic, physical, and emotional burdens experienced by survivors, family members, 

and care givers. 

■ Test community-based interventions in new settings to determine their efficacy and potential 

to be replicated across populations in a culturally appropriate manner. 
18 THE NATIONAL CANCER INSTITUTE 

Patient Navigator Programs Provide Encouragement and Hope to Cancer Patients 

There are too many people who receive a cancer diagnosis either too late for effective 

early treatment or with limited personal resources to take advantage of the quality 

cancer care that is available today. The diagnosis itself can be overwhelming, but 

when coupled with seemingly insurmountable infrastructure barriers, it can destroy 

motivation to regain health. NCI is piloting an innovative program for placing patients 

in contact with “patient navigators” who help individuals and their families work with 

an often complex healthcare system. 

Patient navigators are experienced advocates from local communities – e.g., lay 

people, social workers, and nurses – who are able to communicate credibly with 

the patients. They work with vulnerable or disadvantaged people to help them 

obtain accurate information on diagnosis and treatment procedures, access to hospitals and clinics, guidance 

on financial assistance, and help with tracking their records and obtaining prescriptions. In some cases they 

also arrange for language translation, travel, social support, or religious counseling. 

In support of these programs, NCI is initiating an educational program for patient navigators to enhance 

their knowledge of the clinical trial process, how trials are designed, and the clinical trial as an option in 

health care. The goal is to more effectively provide this treatment choice to underserved and minority 

communities. In addition, information will be provided about how to learn about the clinical trials that are 

available, both at NCI and at NCI-supported sites, and how to access them. 

Newly piloted Patient Navigator Programs in Rapid City, South Dakota, and Laredo, Texas, are supplemented 

with funds from NCI to serve large Native American and Hispanic communities, respectively, each with high 

poverty rates.1 Evaluations of these programs will help to identify successful elements, attract collaborators, 

and model other services and programs to reduce the devastation of cancer among older, minority, and 

other medically underserved populations. 

1 crchd.nci.nih.gov/initiatives/#Navigator 

Collaborating for Action 

NCI also continues to support collaborations among investigators to facilitate research, translation, 

and application of interventions such as screening, early detection, and treatment services and 

access to timely and accurate cancer information through community-based programs. These 

efforts build on partnerships with existing NCI-supported centers, networks, and consortia 

and pilot programs such as the Patient Navigator Program.3 With new resources in Fiscal Year 

2006, we will strengthen and expand these relationships to provide valuable tools for reducing 

cancer health disparities. We will: 

■ Fund a minimum of two additional Community Networks to Reduce Cancer Health Disparities 

and support research to expand the use of proven cancer interventions in minority and other 

underserved populations not yet reached by the program.
THE NATIONAL CANCER INSTITUTE 19 

■ Support partnerships and international collaborative studies on the social determinants of 

cancer and cancer disparities through supplements to the NCI-supported Centers for 

Population Health and Health Disparities.4 

■ Support the development and implementation of a tobacco and health disparities research 

network for advancing the understanding of tobacco-related disparities and translating that 

knowledge into practical use by communities. 

■ Continue to support, in collaboration with the National Institute on Aging, research 

partnerships with NCI-designated Cancer Centers to improve early detection, diagnosis, 

prognosis, treatment, and survivorship in persons older than 65.5 

Training Minorities for Cancer Care and Research 

Training programs for minority healthcare providers and scientists, such as the Comprehensive 

Minority Biomedical Program,6 will increase the number of people prepared to address cancer 

health disparities in their programs and communities. With increased resources in Fiscal Year 

2006, we will: 

■ Develop, implement, and evaluate education 

and training programs designed to create a 

diverse and culturally competent research and 

cancer care workforce. 

■ Support the development of training and 

workshops designed to diversify the cadre of 

mid-career level cancer investigators, expand 

their understanding of the characteristics of 

different cultures, and apply that knowledge 

to research for improving the health of 

specific populations. 

■ Create collaborations between the Minority 

Institution/Cancer Center Partnership program 

and the Community Networks to Reduce 

Cancer Disparities for the creation of joint 

health disparities training programs.7 

1 www.hhs.gov/chdprg 

2 crchd.nci.nih.gov/initiatives/#Special 

3 crchd.nci.nih.gov/initiatives/#Navigator 

4 cancercontrol.cancer.gov/populationhealthcenters 

5 cancer.gov/newscenter/pressreleases/AgingGrants 

6 minorityopportunities.nci.nih.gov/index.html 

7 minorityopportunities.nci.nih.gov/institutions/miccp.html 

Overcoming Cancer Health Disparities 

Budget Increase Request for Fiscal Year 2006 

Determining the causes & extent of cancer 

health disparities $19.00 M 

Studies/think tanks on genetics & race/ethnicity 

Multidisciplinary intervention studies 

New approaches for data collection & sharing 

Community-based research & partnerships 

Studies of & support to specific population groups 

Evaluating promising new interventions 10.50 M 

Tobacco cessation 

Survivorship 

Culturally appropriate interventions 

Collaborating for research, translation, & application 6.00 M 

Social determinants of disparities 

Tobacco-related disparities 

Interface of aging & cancer 

Training minorities for cancer care & research 3.00 M 

Diversity in workforce 

Cultural competence 

Management and support .65 M 

Total $39.15 M
20 THE NATIONAL CANCER INSTITUTE 

Investments in the Strategic Development of Cancer Interventions 


Our Goal Optimize the transfer, development, and delivery of highly effective molecularly 

targeted drugs and technologies to specifically prevent, detect, diagnose, and treat 

cancer. 

One of NCI’s key strategies to accelerate progress against cancer in the next decade is to optimize 

the development and speed the delivery of new targeted cancer diagnostics, therapies, and 

preventives to patients. Accomplishing our aggressive but achievable objectives in this area will 

require a truly seamless national system for taking new cancer drugs and diagnostics from 

preclinical development through commercialization. 

While numerous academic laboratories are focused on cancer drug and biomarker discovery, the 

lack of a robust system and infrastructure for developing these new technologies means that 

many will never reach patients. Developing and obtaining regulatory approval for a single new 

therapeutic drug is estimated to take 10 to15 years at a cost of over $800 million. These barriers 

have prompted the Nation’s pharmaceutical industries to focus their efforts primarily on markets 

of a billion dollars or more and, given the many types of cancer and the potential for large 

numbers of molecular targets for each, cancer does not represent a major market for most large 

pharmaceutical companies. Conversely, the biotechnology industry has embraced the cancer 

market and currently there are over 1,500 biotechnology companies, many of which are focused 

on the development of innovative interventions for cancer. Unfortunately, many of these 

companies do not succeed due to a lack of funding from the capital markets. 

Strategically Expanding Ongoing Activities 

NCI has critically examined the strategies and actions required to optimize the transfer of 

potentially paradigm shifting laboratory discoveries into and through development for targeted 

cancer drugs and technologies, and we have already undertaken specific activities to address some 

of the barriers. Current NCI investments such as the Cancer Genome Anatomy Project (CGAP), 

Academic Public-Private Partnership Programs (AP4s), the Specialized Programs of Research 

Excellence (SPOREs), Rapid Access to Intervention Development (RAID), Rapid Access to 

Preventive Intervention Development (RAPID), and the cancer Biomedical Informatics Grid 

(caBIG)1 are part of an overarching strategy to lower the risks associated with developing new 

cancer interventions. This strategy will be optimized by continued investments in advanced 

bioinformatics platforms, cancer imaging, and nanotechnology. (See pages 32-39.) All of these 

initiatives will drive an ever increasing need for a new, more responsive clinical trials system that 

is focused on the evaluation of targeted, safe agents and devices. (See pages 28-31.) We will use 

new resources in Fiscal Year 2006 for strategic expansion of selected ongoing activities. We will: 

■ Expand the number of new drug candidates arising from the National Cooperative Drug 

Discovery Groups (NCDDG) and the Drug Development Group (DDG).2 

■ Expand the RAID and RAPID programs through NCI’s scale-up capabilities and increased 

use of existing resources in cancer and academic medical centers. 

■ Fund up to six AP4s to discover new interventions for understudied malignancies and rapidly 

translate these discoveries to human clinical trials. 
THE NATIONAL CANCER INSTITUTE 21 

Speeding Development of Molecularly-Based Interventions 

To further facilitate the creation of new molecularly-based diagnostics, therapeutics, and 

preventives and provide critical scientific support for areas such as combination therapies and 

target discovery and validation, NCI must also make investments in new enterprise initiatives. 

Biospecimen Initiative. In an era of exciting discovery about the genomic basis of cancer, 

researchers have identified lack of access to high quality biospecimens as rate limiting to 

progress in molecular medicine. To use sophisticated assay methods such as genomic sequencing 

and protein detection and measurement, a highly reliable source of biospecimens that are 

linked to validated clinical information is essential. With sufficient funding in Fiscal Year 2006, 

NCI will develop a pilot resource for an integrated system to collect biospecimen and clinical 

information and make it easily available to the scientific community. We will: 

■ Provide a standardized system for specimen acquisition, annotation, processing, and storage 

to support genetic and proteomic research and biomarker discovery and validation. 

■ Establish a state-of-the-art information system to link investigators to specimens and foster 

exchange of data across the research enterprise via the cancer Biomedical Informatics Grid 

(caBIG). 

■ Provide a test-bed for broader applications of a new era system for biospecimen banking and 

clinical information management. 

Cancer Genome Analysis Program. Now armed with the genomic code developed through 

the Human Genome Project, researchers are developing technologies that can rapidly and 

inexpensively sequence regions of genomic information as they seek to identify the genetic 

basis of each patient’s cancer. For the patient and healthcare provider, this sets the stage for a 

revolutionary approach to cancer care in the next decade. Identifying the genomic code of 

patients at risk for cancer or aiding in the classification of cancer by the patterns of genes 

present in a tumor will bring an era of molecular medicine not yet explored. 

The Cancer Genome Anatomy Project (CGAP) has provided the cancer research community 

with an invaluable source of state-of-the-art technologies, tools, and databases that has 

contributed significantly to our understanding of key genetic changes in cancerous versus normal 

cells. This information has provided cancer researchers with early direction in their search for 

molecularly-based targets for new cancer interventions. NCI will further extend the scale and 

scope of CGAP through a collaborative program that will systematically investigate and catalogue 

genetic abnormalities across several tumor types using a variety of approaches including gene 

re-sequencing and array technologies. 
22 THE NATIONAL CANCER INSTITUTE 

In Fiscal Year 2006, NCI will support the first patient oriented research project aimed at 

systematically developing genomic data from cancer cells, to set the stage for a large scale 

program. Specimens will be collected from patients along with highly accurate and protected 

patient information. The tumor specimens will be carefully prepared for genomic sequencing 

using the most advanced genomic technology platforms available. In the pilot phase, researchers 

will search for abnormalities in the genetic code of a limited number of human tumor types. 

Several types of sequencing technologies will be applied to the same specimens to determine 

which methods are most efficient and yield the highest quality information. Researchers will 

also identify patterns of abnormal genes in the tumor specimens and investigate the basis of 

cancer and the stages of cancer development. With initial success, this project will be expanded 

to additional types of solid and hematologic tumors. 

Readily Available Biospecimen Resources Are a Must for Cancer Research 

Scientists depend on the availability of high quality biospecimens collected 

in a standard manner – e.g., blood and tissue samples – from cancer 

patients, as well as from healthy volunteers, to enable their research. 

Access to these high quality biospecimens is especially critical in areas 

such as genomics and proteomics investigations and for: 

■ Investigating normal and malignant tissue microenvironments. (See 

pages 43-45.) 

■ Clarifying the underlying biological relationships between anti-tumor 

immune responses and autoimmune responses to immunotherapy. 

(See page 45.) 

■ Identifying and validating biomarkers of precancers for use in cancer 

screening and early detection. (See page 10.) 

■ Developing and validating surrogate molecular endpoints for clinical trials. (See page 30.) 

NCI has historically supported a large number of “bio-banks,” ranging from a few biospecimens in the 

hands of individual investigators to large collections that are available for broad use by the research 

community. We must act now to better standardize and coordinate the collection and storage of human 

biospecimens to allow more widespread and productive use of these precious resources. The collection of 

fresh tissue samples will be pivotal to genomics/proteomics research. These critical samples must be 

collected in full compliance with genetic privacy protection and annotated to include as much data as 

possible about the biospecimen and the case and be broadly available to researchers. 

NCI has collaborated with others to develop a model for a national biospecimen network and accompanying 

database to begin to address the problem of standardization for biospecimens, access, data availability, 

and privacy protection. The network will be pre-competitive, regulatory-compliant, genetic privacyprotected, standardized, and inclusive. As we move ahead with this initiative, we will work to ensure that 

the common standards of collection and storage and peer-reviewed availability of specimens, specified by 

the national concept, are fully integrated into NCI’s biospecimen resource banks. This model is in keeping 

with similar strategies being pursued in other countries such as the United Kingdom and Japan.
THE NATIONAL CANCER INSTITUTE 23 

Sufficient resources in Fiscal Year 2006 will allow NCI to: 

■ Develop a comprehensive database of genomic sequence data from a defined set of human 

tumor types. 

■ Provide data analysis tools to help researchers begin to efficiently sift through millions of 

genomic codes to find relevant signals of cancer development. 

■ Develop improved approaches to sequencing technology that will streamline its application 

into clinical medicine. 

■ Provide new databases that will inform and drive the discovery of new targeted agents for 

cancer. 

Building Capacity for Early Detection and Targeted Treatment 

NCI will also apply new resources in Fiscal Year 2006 to strategic initiatives that build capacity 

for targeted intervention development, to help ensure that the numbers of new targeted drugs 

and devices, developed and ultimately approved for marketing through the FDA, increase 

exponentially in the next few years. 

Biomarkers for Drug Discovery and Early Detection. Biomarkers include a number of biological 

molecules such as DNA and proteins, but one of the most promising areas for drug and device 

discovery and development is the field of proteomics. Recent breakthroughs are enabling 

scientists to identify patterns of protein markers associated with cancer initiation and 

progression and with particular cancers. Biomarkers in cancer research hold promise for making 

“personalized” medicine a reality. They have many potential applications including early 

diagnostic testing, monitoring response to treatment, detecting metastatic disease, and building 

“designer” therapies. When sufficiently validated, they will enable scientists to more rationally 

discover and develop drugs and quickly identify patients that will respond to specific therapeutic 

interventions. Biomarkers are also integral to new cancer detection strategies. In fact, proteomics 

may well hold the key to diagnosing cancer early and finding recurrence well before it becomes 

a threat. With increased resources in Fiscal Year 2006, NCI will develop a new Clinical Proteomics 

and Biomarker Discovery Program to: 

■ Assess technologies central to biomarker discovery and integrate the best performers into 

an optimized platform against which new technologies can be tested. 

■ Develop an open source suite of tools to facilitate the standardization of analysis across 

laboratories and allow meaningful comparison of results. 

■ Establish and make publicly available a comprehensive database for storing the data from 

various biomarker projects. 

■ Provide a central, virtual source for reagents with quality control and timely access to data on 

reagent performance and quality. 
24 THE NATIONAL CANCER INSTITUTE 

An NCI-FDA Partnership Is Paying Big Dividends in Targeted Cancer Drug and Device Development 

Despite increased spending on biomedical research and development, there are fewer new medical products 

reaching consumers than at any time in more than a decade. Our Nation is also facing unprecedented 

challenges involving affordability and access to currently available treatments for all patients. To address 

these issues, the U. S. Food and Drug Administration (FDA) and NCI announced, in November 2003, the 

development of a system for submitting investigational new drug applications (INDs) electronically under 

NCI’s cancer Biomedical Informatics Grid (caBIG) project. This will allow the FDA to review applications 

faster and get new treatments to patients more quickly and at lower cost. The eventual goal of the caBIG 

project is to have an entirely electronic system for the submission and evaluation of clinical information for 

cancer trials. As a first step, NCI and the FDA will work together to build tools that facilitate electronic 

interaction, focusing in particular on IND applications. 

In July of 2004, the FDA created the Office on Oncology Drug Products, which will focus on a strong 

approach to the drug and therapeutic biologics review process. NCI will work with FDA through this and 

other mechanisms to develop processes to ensure that positive results are more quickly translated into new 

diagnostic or treatment options for patients. The formation of the FDA/NCI Interagency Oncology Task 

Force (IOTF) is one such initiative. This joint agreement will enhance the efficiency of clinical research and 

scientific evaluation of new cancer medications and allow researchers to share knowledge and resources. 

The IOTF is currently working to speed progress along the pipeline of targeted cancer interventions by: 

■ Building a cadre of experts in the science of regulatory review of oncology technologies. 

■ Establishing a senior leadership group to triage issues from NCI-supported investigators and consult on 

regulatory submissions. 

■ Integrating common bioinformatics tools, including platforms for reporting clinical trials and electronic 

filing of INDs. 

■ Identifying potential clinical endpoints, from areas such as functional imaging and biomarkers, for use in 

assessing the effectiveness of new agents in clinical trials. 

■ Developing roadmaps for the future regulation of advanced technologies. 

Another joint initiative is the Cancer Fellowship Training Program, which will develop a corps of physicians 

and scientists who are expert in clinical research, the regulatory process, and translation of research 

breakthroughs to clinical practice. New programs will make various training opportunities available for NCI 

researchers at the FDA, including training as product reviewers. 
T H E N A T I O N A L C A N C E R I N S T I T U T E 25 

National Molecular Target Validation and Credentialing Program. Our increasing ability to 

“interrogate” the human genome to determine both the sequence and functions of genes and gene 

products is providing the foundation for new screening technologies designed to identify targeted 

drug candidates. These new technologies range from the use of small chemical probes (chemical 

genomics) to systems that detect specific pathway effects following perturbation with a candidate 

agent. These new systems will significantly enhance the amount of information that can be derived 

in early discovery concerning significant parameters such as toxicity. Another key barrier to 

capitalizing on the discovery and development of targeted cancer agents is the validation of 

molecular targets. We know that cancer may offer literally thousands of potential molecular 

targets, but it is critical that each molecular entity be validated in terms of its potential to become 

a robust target for the discovery and development of highly effective cancer drugs. With new 

resources in 2006, NCI will: 

■ Make available to the community enhanced screening systems to better identify targeted agents 

for cancer. 

■ Establish a pilot program to evaluate target validation strategies such as RNA interference 

(RNAi) and systems biology. 

Streamlining Preclinical Development 

Preclinical development of prospective drugs and diagnostic technologies will require enhanced 

infrastructure including more accurate, predictive, efficacy models; rational processes for selection 

of lead candidates; and new NCI capabilities for process scale-up, as described above. Often 

the most difficult phase of the development of cancer therapeutics and diagnostics is the 

preparation and presentation of the preclinical information required by the FDA to file an 

investigational new drug application (IND). 

The preclinical phase can be daunting and 

expensive, especially for academic investigators 

with limited resources. NCI will use new 

resources in Fiscal Year 2006 to provide support 

for preclinical development. We will: 

■ Establish an integrated preclinical development 

program that places significant emphasis on 

new approaches to define the pharmacology, 

toxicology, distribution, and other significant 

parameters associated with the administration 

of small molecules and biologics. 

■ Make available to the community new 

technologies such as pharmacogenomics and 

metabolomics as part of a new approach to 

preclinical development. 

1 cgap.nci.nih.gov, spores.nci.nih.gov, dtp.nci.nih.gov/docs/raid/ 

raid_index.html, cancer.gov/prevention/rapid, cabig.nci.nih.gov 

2 dtp.nci.nih.gov/docs/ddg/ddg_descript.html 

Strategic Development of Cancer Interventions 

Budget Increase Request for Fiscal Year 2006 

Expanding ongoing activities $20.00 M 

Increased number of new drug candidates 

New interventions for understudied malignancies 

Speding development of molecularly-based interventions 40.00 M 

National biospecimen resource 

Large scale cancer genome analysis program 

Building capacity for early detection & targeted treatment 35.00 M 

Clinical biomarkers discovery & development program 

National molecular target validation/credentialing program 

Streamlining preclinical development 22.00 M 

Infrastructure for preclinical development 

Molecular screening technology platforms 

Management & Support 2.00 M 

Total $119.00 M
Building Research Teams of the Future 

NIH and NCI Find New Ways to Support Interdisciplinary Team Science 

Increasingly, scientists must be able to work in interdisciplinary teams to understand and fully explore the interplay 

among environmental, lifestyle, genetic, and molecular variables contributing to cancer and take advantage of the 

technological resources available to help them do this. 

NIH Roadmap initiatives for building Research Teams of the 

Future are designed to foster team science by making it easier for 

scientists to work across disciplines and organizations. NIH will 

redirect resources to train scientists in interdisciplinary strategies, create specialized centers to 

help forge innovative and more advanced disciplines from existing ones, and plan forward 

looking conferences to catalyze collaboration among the life and physical sciences. New 

funding mechanisms will grant principal investigator status to all key members of a research 

team, provide research funding to multiple institutions, require integrated reviews of grant 

applications that take into account the melding of the various disciplines, and encourage interdisciplinary teams to evolve in both directed and serendipitous ways. NCI is aligning funding 

mechanisms, organizational culture, and strategic investments to accelerate, interdisciplinary 

and multidisciplinary research. 

Within our NCI 2006 Strategic Investments, interdisciplinary training will play a critical role. 

For example: 

■ Education and training programs in health disparities will help create a research and cancer 

care workforce sensitive to the needs of diverse populations and cultures. 

■ Training opportunities for clinical researchers, oncology research nurses, and basic, clinical, 

and public health teams will foster the development of a cadre of investigators who can work 

between bench and bedside. 

■ Joint training programs with medical and public health schools, new training awards, and 

new curricula will enhance the ability of teams to collaborate effectively in research relevant 

to molecular epidemiology. 

■ Cancer biology training programs will prepare interdisciplinary scientists to build, characterize, 

and validate computational models and to use organotypic culture systems. 

Research partnerships will focus interdisciplinary efforts on such topics as: 

■ The interplay of behavior, chemistry, toxicology, and biology to determine the cancer risk 

potential of reduced-exposure tobacco products. 

■ The mechanisms of energetics, energy balance, and cancer and how they inform approaches 

for the prevention of obesity. 

■ The social and genetic determinants of and community-based interventions for overcoming 

cancer health disparities. 

26 THE NATIONAL CANCER INSTITUTE 
THE NATIONAL CANCER INSTITUTE 27 

■ Interventions to improve early detection, diagnosis, prognosis, treatment, and survivorship in 

persons older than 65. 

■ Normal and malignant tissue microenvironments, their molecular signatures, and the origin 

of the cells and factors that comprise the tumor stem cell and the tumor microenvironment. 

■ The associations of known cancer viruses with cancers not previously linked to these viruses 

and the role of microbial agents in the etiology of human cancers. 

■ The causes of and risks for highly lethal cancers such as pancreatic, liver, and esophageal. 

Numerous established and new NCI initiatives and programs support interdisciplinary teams. 

These include NCI-supported Cancer Centers, the Specialized Programs for Research 

Excellence, the Academic Public-Private Partnership Programs, a new Biospecimen Initiative, the 

cancer Biomedical Informatics Grid and consortium, the Cancer Genetics Network, the Cancer 

Genome Anatomy Project, a new Cancer Genome Analysis Program, new Centers for Cancer 

Nanotechnology Excellence, Centers for Population Health and Health Disparities, Centers of 

Excellence in Cancer Communications Research, a new Clinical Proteomics and Biomarker 

Discovery Program, the Clinical Trials Cooperative Group Program, the Community Clinical 

Oncology Program, new Community Networks to Reduce Cancer Disparities, various consortia 

for interdisciplinary epidemiological studies, the Drug Development Group, the Early Detection 

Research Network, a network of high-throughput genotyping laboratories, In Vivo Cellular and 

Molecular Imaging Centers, Integrative Cancer Biology Programs, the intramural Molecular 

Targets Development Program, National Cooperative Drug Discovery Groups, the Network for 

Translational Research in Optical Imaging, the Minority Institution/Cancer Center Partnership 

Program, a new integrated preclinical development program, new centers for Transdisciplinary 

Research on Energetics and Cancer, Interdisciplinary Research Teams for Molecular Target 

Assessment, and Transdisciplinary Tobacco Use Research Centers. 

NCI Plays a Role in the NIH Roadmap for Medical Research 

The NIH Roadmap for Medical Research, launched in September 2003, consists of far reaching initiatives 

intended to accelerate the pace of life science discovery and translation from the bench into practice. 

The Roadmap is focused on efforts that are beyond the scope of any single NIH Institute and that integrate 

the full spectrum of Institute missions. NIH Director Elias A. Zerhouni has spearheaded the Roadmap – 

with input from over 300 nationally recognized leaders in academia, industry, government, and the public 

– to address major opportunities and gaps in biomedical research. 

NCI is involved in several aspects of the NIH Roadmap for Medical Research, contributing expertise to the 

theme areas that align most closely with the Institute's strategic priorities and overall mission. In addition 

to participating in building Research Teams of the Future, NCI is providing infrastructure, expertise, and other 

resources toward the development of imaging and molecular libraries, centralized resources and services for 

translational research, and Regional Translational Research Centers to accelerate the development of new 

drugs, biomarkers, and treatment strategies. 

For more information, visit the NIH Roadmap Web site at nihroadmap.nih.gov. 
28 THE NATIONAL CANCER INSTITUTE 

Strategic Investments in An Integrated Clinical Trials System


Our Goal Build a highly interactive and optimally coordinated cancer clinical trials system 

that will prioritize and accelerate the development of new interventions and ensure that 

those interventions found to be effective are efficiently and seamlessly incorporated 

into medical practice. 

The 2004 Annual Report to the Nation on the Status of Cancer1 reports that observed overall 

cancer incidence rates dropped 0.5 percent annually while overall death rates from cancer 

dropped 1.1 percent each year from 1993 to 2001. Contributing to these encouraging trends 

are new clinical approaches to cancer prevention, early detection, diagnosis, treatment, and 

quality of life after treatment. The vast majority of these interventions have one feature in 

common: they were rigorously tested in clinical trials. Similarly, the majority of interventions 

arising from research proposed in this document will be tested in clinical trials. 

Each year, NCI provides leadership, resources, and expertise for a clinical trials program that 

spans the entire spectrum of activity – from the discovery of novel molecules to the evaluation 

and application of new agents and interventions. We support trials at the NIH Clinical Center 

and at close to 3,000 other sites across the United States. Over 1,500 NCI-supported cancer 

trials are conducted annually, involving more than 12,000 investigators. With expansion over 

the past five years, our clinical research base has grown and become increasingly productive, 

providing hope for untold numbers of current and future cancer patients. 

As we look to the future, we recognize the need to make our clinical trials system even more 

robust, to anticipate scientific and technological advancements and enhance partnerships and 

collaborations with an interdisciplinary and translational focus. Imaging will play a role not 

only in monitoring treatment but also in identifying patients who are most likely to respond 

to a particular drug or combination therapy. In addition, imaging will play a critical part in 

the pre-clinical screening and validation of new targeted compounds. The clinical trials 

system of the future will facilitate the effective conduct of Phase I clinical trials, better prioritize 

and coordinate large Phase II and III trials,2 and directly address regulatory and other issues 

that affect the timeliness with which clinical trials can be completed and their findings translated 

into practice. 

To make clinical trials more efficient and to accelerate the approval of new interventions 

through the regulatory process, NCI will enhance its working relationship with the Food 

and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) to 

develop more streamlined policies and procedures for the conduct of clinical trials. We will 

build partnerships among disparate NCI clinical trial entities and with industry and promote 

communication among regulatory agencies and clinical trials groups. We must promote 

ongoing and forge new communication networks among clinical researchers and the broad 

community of oncologists. Finally, we need to ensure that the diagnostic and therapeutic 

interventions emerging from clinical trials are used to benefit all populations and contribute to 

reducing health disparities. 
THE NATIONAL CANCER INSTITUTE 29 

Strengthening Scientific Prioritization and Coordination 

One of our objectives is to develop a more effective infrastructure for cancer clinical trials that 

will strengthen scientific prioritization and coordination, thereby improving the timeliness 

with which clinical trials are completed and making the process more integrated, open, and 

inclusive of cross-disciplinary and patient advocate input. With increased resources in Fiscal 

Year 2006, we will: 

■ Strengthen flexible collaborations with industry, FDA, the Centers for Medicare and Medicaid 

Services (CMS), OHRP, and other public, private, academic, and patient advocacy organizations 

to oversee the conduct of cancer clinical trials. 

■ Expand state-of-the-science meetings in disease and multimodality settings not currently 

covered and extend the frequency of meetings of established clinical and scientific thought 

leaders, to identify critical research questions to be addressed by clinical trials and develop 

strategic plans for prioritizing and implementing those studies. 

■ Develop new infrastructure and procedures to standardize, coordinate, and track clinical 

trials development and accrual across all NCI-supported clinical trials venues. 

■ Expand access to centralized Institutional Review Board (IRB) resources and clinical 

research administrative support for all NCI-coordinated multi-institutional clinical trials. 

■ Increase funding for imaging in clinical trials in order to utilize the appropriate imaging tools 

in screening and therapy trials, evaluate new imaging probes and methodologies, enable access 

to the imaging data from trials in an electronic format, and facilitate evaluation of image-guided 

interventions. 

■ Increase funding for data managers, research nurses, biostatisticians, and clinicians, as well 

as other functions associated with NCI clinical trials, to both expand access and improve the 

timeliness for completion of the highest priority clinical studies. 

■ Increase funding for training pathways for clinical investigators, oncology research nurses, 

and basic, clinical, and public health teams to foster the development of a cadre of established 

clinical investigators who can work between bench and bedside. 

■ Pilot new approaches and develop prototypes for clinical trials networks that will improve 

the efficiency, coordination, and integration of our national efforts. 

Importantly, NCI will integrate clinical trials based on a common clinical trials informatics 

platform that will be overseen by, and made available to, the full range of investigators 

working within the cancer clinical trials system. This includes NCI clinical faculty, staff, 

academicians, community physicians, representatives of regulatory agencies and the pharmaceutical industry, research nurses, and patient advocates. In addition, electronic repositories of 

currently obtained imaging data in clinical trials will serve as databases for development of 

future software tools and computer aided design methodologies. (See pages 10 and 35.) 
30 THE NATIONAL CANCER INSTITUTE 

Speeding Agent Development and Biomarker Validation through Clinical Trials 

With adequate resources in Fiscal Year 2006, we will also take critical steps to speed the early 

development of novel preventive and therapeutic agents and to validate biological markers for 

early detection and diagnosis and for determining the effectiveness of treatment. We will use 

these new resources to increase the number of promising agents evaluated in NCI-supported 

clinical trials and to develop new molecular diagnostic and imaging techniques capable of 

predicting therapeutic outcome during those studies. We will: 

■ Establish a program of pilot clinical trials employing novel pharmacologic, imaging, and 

molecular target validation principles that will facilitate new intramural-extramural partnerships 

and speed the early development of cancer therapeutics. 

■ Create broadly based working groups to identify clinically relevant surrogate molecular 

endpoints for clinical trials, develop core facilities to standardize and perform high throughput 

molecular pathologic evaluations of potential biomarkers for prediction from tumor and 

normal tissues collected during NCI-supported randomized clinical trials, and develop resources 

and clinical trial designs to validate these endpoints. 

■ Expand translational research capacity to use a broad range of laboratory-based correlative 

studies more extensively in NCI-supported clinical trials. 

NCI Partners with CMS to Streamline Patient Access to Cancer Drugs 

NCI is partnering with the Centers for Medicare and Medicaid Services (CMS) to improve 

patient access to life saving anti-cancer drugs. Because new prevention and treatment 

therapies and diagnostic procedures must first be approved by the FDA, this NCI-CMS 

partnership will build on an NCI-FDA collaboration to better align the efforts of all three 

agencies.* NCI and CMS are developing a Memorandum of Understanding for working 

together in five areas of technology, science, and patient care. The two agencies will work 

together to: 

■ Identify high priority clinical questions about the optimal use of new technologies and 

a process for conducting post-approval studies. 

■ Define a systematic process for consultation between CMS and NCI for evaluating new diagnostics and 

therapeutics for payment and coverage decisions. 

■ Develop more efficient methods for collecting clinical evidence on new technologies and make this 

information more widely available to physicians, patients, and researchers. 

■ Identify and evaluate emerging technologies so that reimbursement policies will better anticipate their 

promise and expedite their adoption in the marketplace. 

■ Identify opportunities for data and resource sharing aimed at improving quality of care, overcoming health 

disparities, reducing variations in treatment, and improving symptom management and end-of-life care. 

*See page 24 for information on the NCI-FDA collaboration.
THE NATIONAL CANCER INSTITUTE 31 

Expanding the Goals of Clinical Trials 

With adequate resources in Fiscal Year 2006, we will also expand the goals of our clinical trials. 

We will: 

■ Provide incentives to include innovative programs in more clinical trials structures, such as 

patient navigation to increase access to cancer clinical trials for minority and underserved 

populations. 

■ Support efforts to improve recruitment and retention of women and minorities in NCIsupported clinical trials programs. 

■ Increase minority participation in clinical 

trials through an NCI fellowship training 

program for healthcare providers and through 

other forums. 

■ Provide incentives for the enhancement of 

symptom management studies within the 

NCI-supported clinical trials system. 

■ Support the use of informatics systems to 

track and record participant information 

needed by healthcare providers for long-term 

follow-up and care after the completion of 

clinical trials. 

■ Stimulate investigations of the long-term effects 

of cancer treatment and related survivorship 

issues. 

■ Stimulate the use of health related qualityof-life and economic endpoints in NCIsupported Phase III trials. 

Integrated Clinical Trials System 

Budget Increase Request for Fiscal Year 2006 

Strengthening scientific prioritization & coordination $116.00 M 

Flexible collaborations 

State-of-the-science & other planning meetings 

Standardization, coordination, & tracking of trials 

Centralized IRB & administrative support 

Increased use of imaging 

Staffing & training 

New approaches & prototypes for networks 

Speeding novel agent development & biomarker validation 28.00 M 

Trials employing novel validation principles 

Identification of surrogate endpoints & biomarkers 

Laboratory-based correlative studies 

Expanding the goals of clinical trials 24.00 M 

Increased access for minority & underserved populations 

Symptom management studies 

Patient tracking & record keeping 

Studies of long-term effects of treatment 

Use of quality-of-life & economic endpoints 

Management & Support 2.85 M 

Total $170.85 M 

1 A collaborative effort of the American Cancer Society, 

the Centers for Disease Control and Prevention, NCI, 

and the North American Association of Central Cancer 

Registries. seer.cancer.gov/report_to_nation/1975_2001 

2 Phase I trials are studies involving small numbers of 

patients to evaluate how new drugs should be given 

(by mouth, injected into the blood, or injected into the 

muscle), how often, and at what dose level. Phase II trials 

continue to test the safety and efficacy of drugs, usually 

focusing on how effective they are for specific types of 

cancer. Phase III trials test new drugs, new combinations 

of drugs, or new surgical procedures in comparison to the 

current standard. Phase III trials generally enroll larger 

numbers of people and are frequently conducted at multiple sites – e.g., doctors’ offices, clinics, and cancer centers. 
32 THE NATIONAL CANCER INSTITUTE 

Strategic Investments in Advanced Technologies*


Our Goal Accelerate the development of highly effective advanced technologies and 

maximize their use to power and streamline research, enhance the options for patient 

care, and connect investigators with one another and with the healthcare provider and 

patient communities. 

Research over the past three decades has led to unimagined progress in our understanding of 

the cancer process at the genetic, molecular, and cellular levels. As we search for the most effective 

ways to apply these insights to the prevention, early detection, and management of cancer as 

a disease process, we know that our most direct path will be through the optimal integration 

of science and technology. Our Nation’s past successes in creating technologies to enhance 

discovery – from the space program to the Human Genome Project – have produced dramatic 

scientific breakthroughs and advances. Now we have an opportunity to achieve an equally 

unimagined goal: to eliminate the suffering and death due to cancer. 

Today’s technologies and tools are replacing Einstein’s chalk and blackboard with powerful 

computers, sophisticated software, and networking that enables collaboration on a global 

scale. Identifying many of the complex mechanisms responsible for cancer through genetic and 

protein microarrays, molecular imaging, and high throughput screening are proving to be pivotal 

in accelerating our ability to intervene against these processes. Similarly, technology-dependent, 

molecularly targeted therapies based on a patient’s disease-specific profile of markers provide 

hope that the cancer burden will be lightened and patients will enjoy a higher quality of life. 

We are able to make rapid gains against cancer because of the development and availability of 

advanced technologies that enable accelerated research and create effective interventions. 

Bioinformatics 

Hastening Progress against Cancer Using A 21st Century Integrated, Electronic Network 

By using the power of modern information technology, NCI is leading the way in developing 

a bioinformatics platform that promises to revolutionize the biomedical research enterprise. 

Scientists in various disciplines will have access to a common infrastructure for collaboration 

and integration of findings, and new “plug and play” tools developed by the researcher 

community will make it possible for investigators to greatly accelerate their research. For 

example, researchers at Cancer Centers across the country will be able to access data on the 

molecular characteristics of patients with a particular type of cancer who are being treated 

with a specific drug. Diverse data mounted on common platforms will permit researchers to 

use innovative analytic tools to mine the information in ways inconceivable a few years ago. 

And researchers can take advantage of “in silico” experiments that facilitate rapid, cost-efficient 

hypothesis generation and evaluation. 

* To further the development of the advanced technologies described here, NCI is proposing a national initiative for coordinating and channeling these efforts across public and private organizations to expedite the delivery of cancer diagnostics 

and therapeutics to patients and their caregivers. See pages 40-41. 
THE NATIONAL CANCER INSTITUTE 33 

Up to the present, bioinformatics resources have been developed in organizational isolation, 

with tremendous variability in rules, processes, vocabularies, data content, and analytical tools. 

NCI will address these concerns and strengthen the potential for bioinformatics integration with 

the cancer Biomedical Informatics Grid (caBIG).1 The caBIG will provide a unifying architecture 

to transparently connect information and tools much like a home entertainment system in 

which components are made by different manufacturers but built to common standards that 

allow users to combine them in various ways. Our long-term goal for bioinformatics is to 

improve the sophistication of information technology use and surmount the barriers that limit 

interaction across research institutions. NCI is currently piloting a core infrastructure with the 

participation of 50 Cancer Centers. 

We are also fostering the development and use of new informatics technology to accelerate, 

better coordinate, and facilitate participation in NCI-supported clinical research. Currently, 

volumes of valuable raw data are not tapped, effective best practices are not widely distributed, 

and resources are wasted because of duplication of effort. With new bioinformatics tools and 

infrastructure, trials will be completed more quickly in multi-institutional settings with uniform 

electronic case report forms and data reporting systems. Databases and analytical tools will 

make information from all clinical trials available to NCI-supported researchers for efficient 

patient accrual, information retrieval, and data analysis. Informatics systems will assist the 

cancer community with priority setting and allow for fuller participation and a more transparent 

decision making process. Advocacy groups and individual patients will be empowered to 

participate in clinical research and to authorize use of materials for basic science investigations. 

Confidential clinical and proprietary information will be protected by controlled, secure 

access. Just as e-business models have transformed the American market place, the caBIG 

platform will overcome traditional institutional limitations. Community practitioners, clinical 

research organizations, and academic centers will be linked through this new model of clinical 

research. Healthcare providers will become full partners in the research enterprise and educated 

consumers of research findings. 

We will use funding increases for bioinformatics in Fiscal Year 2006 to: 

■ Evaluate the prototype caBIG at the pilot centers and expand the data, software, and 

infrastructure available through the Grid. 

■ Expand the development process and extend participation in the caBIG consortium to other 

cancer research institutions around the country. 

■ Develop and evaluate a World Wide Web-based, clinical research outcomes reporting system 

with voluntary participants from Specialized Programs of Research Excellence (SPOREs), 

Cancer Centers, and the intramural Center for Cancer Research (CCR).2 

■ Expand World Wide Web-based, clinical trials support infrastructure through a pilot study 

in conjunction with the CCR trials group, selected inter-SPORE collaborations, and Cancer 

Centers. 

■ Develop infrastructure and tools, including an Internet resource, that facilitate community-wide 

clinical research participation and support. 
34 THE NATIONAL CANCER INSTITUTE 

caBIG Aligns with REMBRANDT to Power Translational Research 

Primary brain tumors are a leading cause of cancer mortality in children and young 

adults and the incidence of brain tumors (gliomas) in older people is increasing. Effective 

therapeutic options are limited with many patients dying of their disease within a year of 

diagnosis. Patients, who survive, face devastating effects of the tumor and treatments 

that impact cognition, function, and quality of life for themselves and their caregivers. Novel 

therapeutic approaches are desperately needed. REMBRANDT, 1 a partnership between 

NCI and the National Institute of Neurological Disorders and Stroke (NINDS), is an initiative 

to create a publicly available database that will house biologically and clinically oriented 

data regarding primary brain tumors. By using this data to develop novel molecular 

classification systems, this partnership can move us toward an era of individualized 

cancer treatment based on the molecular genetics of each patient’s tumor. 

To accomplish this goal, REMBRANDT will be designed to house two sets of valuable 

data. The first set of data will come from the NCI-sponsored Glioma Molecular Diagnostic 

Initiative (GMDI), a prospective clinical trial and the largest genetic/clinical corollary study ever conducted. 

Hundreds of brain tumor patients throughout the country undergoing surgery will have samples of their tumors 

sent to NCI for exhaustive genetic and molecular analysis and the findings will ultimately be correlated with 

the clinical course of the individual patient. The second type of data housed by REMBRANDT will be a wide 

array of molecular and genetic data regarding all types of primary brain tumors. REMBRANDT will be the 

vital link that will not only allow disparate types of data to be housed in a single place, but will also supply 

the bioinformatics tools critically necessary for the useful analyses of such data. 

NCI’s Cancer Biomedical Informatics Grid, (caBIG), offers a library of tools and resources to initiatives such 

as REMBRANDT to facilitate integrative analysis from bench to bedside and back. The new molecular 

glioma classification system that will result from GMDI and REMBRANDT will be biologically based, giving 

insight into pathology and helping physicians to predict responsiveness to specific therapies. Crosstalk 

between REMBRANDT and caBIG will serve all initiatives. caBIG and NCI will contribute tools to REMBRANDT 

and the research community will be able to access REMBRANDT resources through an NCI developed 

WWW portal. 

How does caBIG work? In Cancer Centers, developers and adopters collaborate in “workspaces” to develop 

and apply tools, systems, and data elements that enable integration and sharing of information. In the 

REMBRANDT initiative, clinical data to be acquired includes progression of the tumor and survival of the 

patient, treatment and response, toxicity, imaging parameters, and pharmacology. Populating the database 

with molecular and genetic data will help identify and analyze patient genetic profiles, molecular pathways 

of cancer progression, novel molecular targets, and patient-specific tailored therapy. Researchers can 

explore how genetic changes correlate with the patient’s response to therapy and overall survival within 

given age groups, geographical locations, and ethnicities. The database is planned for development over a 

three-year timeline and will be fully open and accessible to all investigators, both intramural and extramural. 

1 REMBRANDT, REpository of Molecular BRAin Neoplasia DaTa
THE NATIONAL CANCER INSTITUTE 35 

Cancer Imaging 

Improving Our Understanding of Cancer Biology and Facilitating Cancer Preemption and 

Clinical Management of Cancer and Cancer Risk 

Clinicians are increasingly relying on imaging methods as biomarkers for cancer risk and 

treatment efficacy. Image guided cancer intervention is a rapidly evolving area that may be 

used to cure some cancers and precancerous lesions, and also to provide minimally invasive, 

well-tolerated palliative therapies. Imaging informatics optimizes the availability and effectiveness 

of cancer imaging data in research as well as clinical environments. Imaging methods are used 

hand-in-hand with emerging technologies such as nanotechnology, proteomics, and high 

throughput screening to identify cancers earlier and help assess the effectiveness of therapy. 

Imaging of small animals used in research, particularly genetically engineered mice, is increasingly 

recognized as a powerful discovery tool in cancer research. As our knowledge of the molecular 

basis of cancer increases, molecular imaging methods are providing clinicians with telling 

details about the environs of patients’ tissues. With increased resources for cancer imaging in 

Fiscal Year 2006, we will: 

■ Establish publicly available image archives, linked to outcome and other clinical data, and 

partner with industry to support image archives. 

■ Integrate image-guided intervention research into Cancer Centers, Specialized Programs of 

Research Excellence (SPOREs), and NCI’s Center for Cancer Research (CCR). 

■ Use nanotechnology to design “smart” injectable, targeted contrast agents that improve the 

resolution of cancer to the single cell level. 

■ Engineer nanoscale devices capable of addressing the biological and evolutionary diversity 

of the multiple cancer cells that make up a tumor within an individual. 

■ Expand the Small Animal Imaging Resource Program, the Network for Translational Research 

in Optical Imaging, and the Development of Clinical Imaging Drugs and Enhancers program.3 

■ Develop a program for imaging validation in animal models. 

We will also use new resources in Fiscal Year 2006 to integrate correlative imaging studies, such 

as monitoring response to therapy, into NCI-supported clinical therapy trials (See page 29.) 
36 THE NATIONAL CANCER INSTITUTE 

Proteomic Technologies Initiative 

Overcoming the Barriers to Early Detection of Cancer 

Scientists are taking new steps to identify profiles, or signatures, of proteins and peptides 

(fragments of proteins) that are found in tumors and often in the circulating blood that signal 

early phases of cancer development. Proteins serve complex and diverse functions in the body, 

from giving structure to our cells to regulating processes such as digestion, respiration, and the 

growth rate of cells. When proteins do not function properly, normal body processes can go 

awry. For example, cancer is caused by errors in proteins that regulate when and how fast 

cells replicate themselves, as well as the timing of cell death. One of the goals in cancer research 

is to develop technologies that measure these abnormal proteins and can eventually be used as 

simple diagnostic blood tests. However, there are some sizeable technical challenges that stand 

in the way of achieving that goal. These abnormal proteins are found in minute quantities and 

the blood contains hundreds of thousands of these proteins. The net effect is that we need to 

refine the technology so that it can find “a needle in the haystack” with unprecedented reliability. 

In 2006, NCI will support development of advanced technology platforms for overcoming these 

barriers and preparing diagnostic methods ready for clinical testing. Mass spectroscopy, a 

favored approach involving high energy lasers, high powered electronic sensing, and computing, 

is used to identify specific proteins and their fragments based on their size and electrical charge. 

Another avenue is to use DNA and antibodies to capture proteins and measure their quantity 

on electronic chips. Patients in the near future may well have small samples of their blood 

analyzed using mass spectroscopy and protein chips that will, within minutes, identify abnormal 

proteins that indicate early, very treatable cancers. 

NCI is developing infrastructure to help researchers speed development of these technologies 

and bring them to the clinic. Through a new Mouse Models of Human Cancers Consortium 

(MMHCC)4 initiative, researchers will create new resources including antibodies, data that 

provide standards for future measurement comparison, serum specimens, and histologic data. 

These resources will enable investigators to develop the technology platforms needed to detect 

proteins at very low levels and serve as a model for testing this approach for clinical medicine. 

With sufficient resources in FY 2006, this program will: 

■ Support two consortia of more than 10 laboratories, each focused on improving protein 

detection platforms important for early cancer detection research. 

■ Provide a publicly available database of protein measurements from more than 20 different 

mouse models of cancer to give researchers a starting point to begin clinical studies. 
THE NATIONAL CANCER INSTITUTE 37 

■ Develop advanced computer software and use it to analyze the immense amount of data 

generated by the project. 

■ Make available a repository of mouse protein antibodies, peptides, and serum as a research 

resource. 

■ Improve the accuracy and precision of mass spectroscopy and antibody detection methods. 

A Treasure Trove of Diagnostic Information 

Late in 2003, NCI scientists and partners reported a 

breakthrough in proteomic analysis that may make 

early detection by protein profiling even more practical. 

These scientists developed a method that enhances 

detection of the smallest proteins found in the blood. 

According to this team of scientists, these small proteins 

represent a “treasure trove of diagnostic information 

that has largely been ignored until now.” The trouble 

is that these small proteins are normally carried 

through the body attached to larger “carrier” proteins. 

Hidden from detection when attached to a carrier 

protein, these small proteins are quickly excreted from 

the body when not bound to a carrier. As a result, 

these small proteins are notoriously difficult to detect 

in blood samples. However, this team of scientists 

has found a way to release small proteins from their 

carriers after blood has been drawn from the patient 

and prior to analysis of the blood sample. This simple, 

but ingenious technique is opening the door for vastly 

improved proteomic profiling techniques that can 

include small, as well as large, proteins in signature 

analysis.
38 THE NATIONAL CANCER INSTITUTE 

Nanotechnology Will Enhance Future Cancer Imaging 

Nanotechnology has emerged as a key strategy for imaging telltale molecular features of cancer that are 

notoriously difficult to detect. One team of NCI-supported scientists is crafting a nano-sized construct to 

identify areas of new blood vessel growth, or angiogenesis, which is characteristic of growing tumors. The 

surface of this construct is designed to interact with specific molecular features indicative of angiogenesis, 

while the core contains thousands of atoms of a paramagnetic element. The paramagnetic properties allow 

the probes to be imaged by Magnetic Resonance Imaging (MRI). In addition, this core may contain other 

signal enhancing agents for improved in vivo detection. The use of such multi-modal probes permits highly 

sensitive imaging of specific molecular features of cancer, with excellent spatial resolution. 

In vitro studies have shown that the same nanoprobe can be used for targeted drug delivery. This image 

shows a targeted nanoprobe in contact with a melanoma cell. The nanoprobe appears red against the 

green background of the cellular fluid. Evidence is mounting that such nanosystems can achieve a marked 

improvement in therapeutic effectiveness, as high concentrations of a drug are delivered to targeted cancer 

cells, while non-targeted cells are spared exposure to toxic concentrations.1 

Another NCI-supported team is investigating in vivo cancer imaging using 

nano-sized “quantum dots” – tiny crystals that glow when they are stimulated 

by ultraviolet light. This team has achieved sensitive, multicolor fluorescence 

imaging of cancer cells in mice using a quantum dots probe that preferentially 

binds to prostate cancer cells. In this in vivo image, the mouse on the left is 

tumor free. A human prostate tumor growing in the mouse on the right shows 

in fluorescent orange-red. 

The structure of this imaging probe makes it well suited to carry diagnostic and therapeutic agents. 

However, researchers must carefully examine toxicity issues before testing this quantum dots application 

in people. 

With focused investment in these and other nanotechnologies, NCI anticipates a future when nanodevices 

will be used to detect cancer at its earliest stages, pinpoint its location within the body, deliver anti-cancer 

drugs specifically to malignant cells, and monitor drug effectiveness. 

1 Image provided by Gregory M. Lanza of Washington University. 

2 Image published in Nature Biotechnology, August 2004, page 972. A special thanks to authors Xiaohu Gao and 

Shuming Nie of Emory University and Georgia Institute of Technology, Yuanyuan Cui and Leland W. K. Chung of Emory 

University, and Richard M. Levenson of Cambridge Research & Instrumentation, Inc.
T H E N A T I O N A L C A N C E R I N S T I T U T E 39 

Alliance for Nanotechnology in Cancer 

Targeting and Modifying Biological Responses at the Subcellular Level 

Nanotechnology offers an unprecedented and paradigm changing opportunity to study and 

interact with normal and cancer cells at molecular and cellular scales, in real time and during the 

earliest stages of the cancer process. Nanotechnology will enhance cancer diagnosis and treatment 

in numerous ways. Imaging agents and diagnostics will allow clinicians to detect cancer in its 

earliest, most treatable, pre-symptomatic stage. Nanosystems will provide real-time assessments 

of therapeutic and surgical efficacy for accelerating clinical translation. Multifunctional, targeted 

devices capable of bypassing biological barriers will deliver multiple therapeutic agents at high 

local concentrations – and with physiologically appropriate timing – directly to cancer cells and 

those tissues in the microenvironment that play a critical role in the growth and metastasis of 

cancer. Nanoscale agents will be capable of monitoring predictive molecular changes and 

preventing precancerous cells from becoming malignant. Novel methods will aid in the management of symptoms of cancer that adversely impact quality of life. And research tools will enable 

investigators to quickly identify new targets for clinical development and predict drug resistance. 

To support and coordinate the cancer nanotechnology programs, NCI has established the Alliance 

for Nanotechnology in Cancer5 to unite a broad array of programs to maximize the technology 

outputs. Our nanotechnology plans place a premium on supporting cross-disciplinary teams that 

partner with existing NCI-supported efforts and 

with the private sector. With adequate resources 

in Fiscal Year 2006, we will continue to build 

the programs of the Alliance. We will: 

■ Support 3-5 Centers of Cancer Nanotechnology Excellence (CCNEs) to serve as hubs 

for the development and application of nanotechnology and nanoscience solutions to the 

diagnosis and treatment of cancer. 

■ Encourage development of multidisciplinary 

nanotechnology research teams and support 

the career development of individual investigators who will become future team leaders. 

■ Support individual projects in cancer nanotechnology platforms for diagnosis, treatment, 

and prevention. 

Advanced Technologies 

Budget Increase Request for Fiscal Year 2006 

Building bioinformatics infrastructure and tools $12.75 M 

The cancer Biomedical Informatics Grid (caBIG) 

Support to NCI clinical trials & community participation 

Developing & applying advanced imaging technologies 18.00 M 

Publicly available image archives 

Image-guided intervention research 

Correlative imaging studies in NCI clinical trials 

Nanotechnology for contrast agents 

Nanoscale devices to address cancer cell diversity 

Supporting a proteomic technologies initiative 50.00 M 

Consortia for improving protein detection platforms 

Protein measurements database 

Advanced computer software for project data analysis 

Improvement of mass spectroscopy & antibody detection methods 

Building the Alliance for Nanotechnology in Cancer 40.00 M 

Centers for Cancer Nanotechnology Excellence 

Multidisciplinary nanotechnology research teams 

Individual projects for diagnosis, treatment, and prevention 

Management & Support 2.05 M 

Total $122.80 M 

1 cabig.nci.nih.gov 

2 spores.nci.nih.gov, cancer.gov/cancercenters, ccr.cancer.gov 

3 cancer.gov/bip/sairp.htm, cancer.gov/bip/ntroi.htm, cancer. 

gov/dip/DCID_des.htm 

4 emice.nci.nih.gov 

5 nano.cancer.gov 
When the National Cancer 

Act was signed in 1971, 

our Nation began a 

journey to defeat cancer. 

Unfortunately, one person 

in this country still dies 

from cancer each minute 

of every hour of every day. 

40 T H E N A T I O N A L C A N C E R I N S T I T U T E 

The National Advanced Technologies Initiative for Cancer 

Harnessing the Power of Advanced Technologies to Eliminate the Suffering and Death Due to Cancer 

Although cancer is being unraveled rapidly at the gene, protein, and 

even the “nano” levels by the largest group of researchers ever to 

investigate a specific disease, we have not concomitantly created 

the technology development resources and the seamless system 

needed to capitalize on their discoveries. 

Urgent Need – Unique Opportunity 

We need to assemble interdisciplinary teams and create innovative mechanisms that enable the exchange of ideas and materials in ways that 

maintain incentives for the commercialization and delivery of these new 

cancer technologies. On a national scale, we need public-private coordination aimed at delivering advanced technologies through an integrated 

pipeline of cancer diagnostics and therapeutics development. 

NCI’s current Cancer Center infrastructure is well established and already plays a central role 

in the development, transfer, and commercialization of advanced technologies. The discovery 

and early development of drugs such as GleevecTM, a molecularly targeted drug for chronic 

myelogenous leukemia, have taken place in these Centers. Cancer Centers have also been pivotal 

in establishing relationships with state and regional biotechnology programs and are logical 

connection points for leveraging resources with private companies and other collaborating 

entities to accelerate the development of advanced cancer technologies. NCI has already taken 

steps to achieve paradigm shifting advances through the launch of the cancer Bioinformatics 

Grid (caBIG), an unprecedented platform to be available to the entire cancer research community. 

We have also undertaken early efforts in areas such as biomarkers and nanotechnology. (See 

pages 32-39.) However, without an initiative such as the one described below, it will likely take 

decades for these technologies to reach patients. 

Proposed Initiative 

The National Advanced Technology Initiative for Cancer (NATIc) will provide the research and 

development community with the necessary infrastructure to harness the Nation’s biomedical 

technology resources and capabilities and speed product development. This effort will capitalize 

on discoveries from basic research and leverage existing technology development capabilities 

nationwide. Through a virtual network of regional “hubs,” the most innovative biomedical 

scientists, clinicians, physical scientists, mathematicians, engineers, and others will be linked in 

cutting-edge collaborations for technology development. Partnerships among academic and 

research institutes, the biotechnology and pharmaceutical industries, and government agencies 

will integrate and coordinate translational application and commercialization and help bridge 

the gap between discovery and delivery.
THE NATIONAL CANCER INSTITUTE 41 

A central coordinating unit will be established to provide core services and integrative technologies 

to the regional hubs. Specialized technology “nodes” will focus on specific areas of research 

and development at cancer and academic medical centers, state and regional innovation and 

biotechnology centers, and start-up and other private sector companies. Examples of specialty 

areas that will benefit from integration and coordination are bioinformatics and advanced 

computing; advanced imaging; drug discovery and high-throughput screening; proteomics, 

biomarkers, and diagnostic platforms; computational and systems biology; nanotechnology; 

high-throughput genomics sequencing; biopharmaceutical development and scale-up; biosensors 

and model systems engineering; and bioengineering and advanced prototype facilities. 

Anticipated Outcomes 

The advanced healthcare technologies that derive from this initiative will provide the Nation 

with a unique resource to not only help NCI achieve its goal but also support research advances 

in other diseases and ultimately accelerate the realization of personalized medicine. With the 

launch of this integrative approach, we anticipate dramatic acceleration in several of the 

strategic investment areas described in this document. 

■ Biomarker studies will be completed more quickly, revealing protein patterns and other 

molecular changes in saliva, sera, urine, or biopsy tissue that indicate the presence of 

precancerous lesions or malignant tumors. 

■ New nanotechnology platforms will more quickly allow for the earlier use of biomarker 

information in diagnosing cancer through a single drop of blood. 

■ Innovations in cancer imaging will move the field more rapidly beyond anatomical imaging 

to methods that detect and monitor the molecular features of cancer. Technological advances 

will speed the availability of new devices and agents for the real-time monitoring of genetic 

and other cancer-associated changes. 

■ Novel approaches built through NATIc collaborations will enable clinicians to optimize the 

use of targeted diagnostics, therapies, and preventives to preempt cancer at its earliest stages 

and deliver the right treatment to each patient. 

■ Common bioinformatics platforms and tools provided through a virtual network will support 

data sharing and allow cross-disciplinary teams to work synergistically to develop and deliver 

advanced cancer technologies. A “smartcard” for storing electronic medical records and 

making them available to clinical trial participants and their caregivers for follow-up care is 

one of the many innovations envisioned by this initiative. 

Required Resources 

The NCI Fiscal Year 2006 budget increase request for Advanced Technologies is summarized on 

page 39. We propose to support the NATIc separately, at a total cost of $2.5 billion over five 

years, through three funding sources: (1) special appropriations from Congress totaling $1.5 billion over the five-year period, (2) redeployment of $500 million of NCI's annual appropriations 

over five years, and (3) $500 million in philanthropic contributions. 
42 THE NATIONAL CANCER INSTITUTE 

Strategic Investments in Integrative Cancer Biology


Our Goal Understand the complex networks within cancer cells and between cancer cells 

and their environment to discover new leads for cancer prevention, detection, diagnosis, 

and treatment. 

Integrative cancer biology is the study of cancer as a complex biological system. Researchers 

in this field seek to understand the dynamic and spatial interactions that exist among molecules 

in a cell, among cells, between cells and their “microenvironment,” and between the organism 

and its “macroenvironment.” These interactions are potential targets for new and more 

rationally designed interventions to prevent, detect, diagnose, and treat cancer. Our integrative 

cancer biology initiatives focus on creating computational models of the complex networks 

within and among cancer cells, building our understanding of the tumor microenvironment, 

and studying the role of the tumor macroenvironment in cancer development. To carry out these 

initiatives, cancer biologists will depend heavily on a multidisciplinary approach. Expertise in 

the computational sciences and collaborations with scientists in other fields that study complex 

systems will be essential. Researchers will also need animal models that mimic the development 

of cancer in humans and powerful new tools for imaging molecular interactions, integrating 

large datasets, and validating computational models. 

Developing Computational Models of Cancer 

With increased resources in Fiscal Year 2006, NCI will expand efforts to build models of 

the complex networks within and among cancer cells. Scientists know that a cell becomes 

malignant as a result of changes to its genetic material and that accompanying biological 

characteristics of the cell and its surrounding microenvironment also change. Genetic mutations 

in an evolving cancer cell result in proteins that do not function correctly. These dysfunctional 

proteins disrupt the intricately balanced molecular communication networks of the cell. Using 

data derived from research on the tumor micro- and macroenvironments, scientists will create computational models of these complex networks to help develop new ways to preempt 

the development and progression of cancer. New NCI-supported Integrative Cancer Biology 

Programs (ICBPs)1 have already begun the development of reliably predictive computational models of cancer initiation, promotion, and progression; the integration of experimental and computational approaches for understanding cancer biology; and the support of integrative cancer biology as a distinct field. To further the development of computational models, we hope to: 

■ Increase the number of ICBPs. 

■ Fund collaborations with the ICBPs to enable the research community to apply the approaches 

of integrative biology. 

■ Establish programs in integrative cancer biology to train interdisciplinary scientists to build, 

characterize, and validate computational models. 

■ Provide additional funding for the Mouse Models of Human Cancers Consortium2 to (a) 

accelerate the pace at which accurate, reproducible mouse models of human cancers are made 

available, and (b) define the process for using these mouse models to validate computational 

models of complex cellular networks and to evaluate targeted therapeutics. 
THE NATIONAL CANCER INSTITUTE 43 

■ Expand the imaging acquisition and integration capabilities of the Integrative Cancer 

Biology Programs and the Mouse Models of Human Cancers Consortium to develop (a) 

novel cancer imaging agents, nanoparticles, and technologies for use in cells and small animal 

cancer models, and (b) methods for effectively integrating imaging data with genetic, 

molecular, and cellular data. 

■ Expand the intramural Molecular Targets Development Program3 to accelerate discovery of 

compounds that can serve as bioprobes for functional genomics, proteomics, and molecular 

target validation research as well as leads or candidates for drug development. 

Understanding the Tumor Microenvironment 

In Fiscal Year 2006, NCI will also extend efforts to understand the tumor microenvironment, 

which is the local and systemic architecture surrounding a cancer cell. The microenvironment 

includes other cells; growth factors; enzymes; and parts of the blood, lymphatic, and immune 

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 cancer cells, the body’s 

processing of treatment agents, and the development of resistance to cancer treatments. Therefore, 

research to understand the tumor microenvironment more fully may provide additional targets 

for preempting cancer and better methods for treating it. This research will characterize molecular 

signatures of cells in the tumor microenvironment as well as the dynamic communication among 

these cells; interactions between cells and factors in the macroenvironment that predispose 

individuals to cancer; and interaction between the immune system and the cancer cell during 

cancer initiation, promotion, and progression. The latter interaction will establish the roles 

of both the innate inflammatory responses and adaptive immune responses in promoting and 

controlling tumor formation. 

Computational Modeling Has Multiple Applications for Cancer 

Computational modeling is a central feature of integrative cancer biology studies aimed at generating 

predictive and testable models of cancer. Computational biologists are developing computer programs that 

use complex, interactive calculations to analyze massive amounts of data about cancer cells and their 

micro- and macroenvironments. These modeling programs use combinations of simple statistical tests, data 

mining applications, and higher-order mathematical equations. They are similar to those used by meteorologists to help predict the weather, by economists to predict future trends, and by engineers to design 

complex modern aircraft. Molecular scale models are being designed, for example, to describe the folding 

patterns1 of critical cancer proteins. Computational models also might be used to study the response of a 

cancer patient’s immune system to a developing tumor. Researchers anticipate that computational models 

for cancer, once refined and validated, will not only yield insights and knowledge about cancer, but will also 

be used to help diagnose cancer patients and to plan and monitor treatment strategies. 

1 In protein synthesis, a series of amino acids are sequentially attached to one another to form a long chain. This linear 

chain then folds upon itself to form a protein with the correct shape to perform its particular function in the cell. 
44 T H E N A T I O N A L C A N C E R I N S T I T U T E Courtesy of the National Institute on Aging 

Understanding the Biology of Aging and Cancer 

Older patients differ from younger cancer patients in susceptibility to disease progression and response 

to treatment. The underlying mechanisms of cancer and aging overlap in the study of tumor initiation, 

progression, and maintenance. NCI and the National Institute on Aging (NIA) have partnered to invigorate 

the research community’s interest on the intersection of aging and cancer. Studies on the biology of aging 

and cancer are fundamental to this endeavor. Researchers supported by the NCI/NIA partnership 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. Teams of researchers will investigate: 

■ Genetic change, environmental influences, and host factors such as oxidant stress and cell death that 

may alter tumor progression in the aging patient 

■ The interaction of normal aging cells and cancer cells within the tumor microenvironment 

■ Differences in manifestation of cancer types in older and younger patients 

■ Cellular and molecular characteristics that distinguish between those patients who could benefit from 

aggressive therapy and those who could be spared further therapy 

■ Molecular alterations in carcinogenesis that are related to aging cells 

■ The potential short- and long-term medical effects induced by treatment, such as susceptibility of the 

older patient to multiple primary tumors, anti-tumor drug alterations, and cancer recurrence 

■ The human biology of cancer and aging that reveal which aspects of tumor biology and tumor growth 

vary by age 

This research will also provide necessary data for development of the computational models of 

interactions between the tumor and its microenvironment. To extend our understanding of the 

tumor microenvironment, we will: 

■ Establish a multidisciplinary alliance of researchers, engineers, and bioinformatics experts to: 

— Create technical resources that will facilitate the visualization of stromal components at the 

molecular and cellular levels and the establishment of a repository of normal stromal cells 

and matrix molecules. 

— Investigate the normal and malignant tissue microenvironments, identify their molecular 

signatures, and identify the origin of the cells and factors that comprise the tumor stem cell 

and the tumor microenvironment. 
THE NATIONAL CANCER INSTITUTE 45 

■ Fund grant supplements to train investigators to use organotypic culture systems that 

accurately model the interaction between the cancer cell and the microenvironment and make 

these systems readily accessible to the research community. 

■ Support the development of strategies for investigating, manipulating, and monitoring/imaging 

in vivo human immune responses to cancer. 

■ Support studies to clarify the underlying biological relationship between anti-tumor immune 

responses and autoimmune responses to normal cells/tissues in humans undergoing cancer 

immunotherapy. 

■ Expand the availability of resources to academic laboratories for small molecule and biologics 

development through the Rapid Access to NCI Discovery Resources (R*A*N*D) program.4 

Defining the Role of the Tumor Macroenvironment 

In addition to seeking to understand the interactions among molecules in a cell, among cells, 

and between cells and their microenvironment, integrative cancer biology also addresses the 

role of the tumor macroenvironment. This includes the poorly understood effects of an 

individual’s exposure to various elements in the environment such as unhealthy air and water 

and the influence of lifestyle factors such as diet, obesity, physical activity, and tobacco use. 

Research on the tumor macroenvironment also includes studies of certain microbial agents that 

are known to be closely associated with the etiology of some cancers (e.g., HPV with cervical 

cancer; HBV and HCV with liver cancer; EBV with breast cancer; helicobacter with stomach 

cancer). The mechanism by which these agents increase risks for cancer is not firmly established, 

and scientists continue to explore the extent to which other known or unknown viruses or 

microbes may impact cancer development and progression. Research on these topics will be 

critical to developing new interventions and tools for preventing, detecting, diagnosing, and 

treating cancer. With sufficient resources in Fiscal Year 2006, we will: 

■ Establish collaborative research groups to explore, characterize, and validate associations of 

known cancer viruses with cancers not previously linked to these viruses (e.g., study the role 

of human papillomaviruses in squamous cell esophageal and non-melanoma skin cancers). 

Characterize the role of microbial agents in the etiology of human cancers such as leukemia, 

lung cancer, and non-Hodgkin’s lymphoma. 

■ Support studies of the role of microbial agents in tumor development by investigating 

(a) viral latency and reactivation, (b) the microbial flora of stromal cells, and (c) the 

anti-microbial inflammatory response. Included will be studies on immunosuppressed 

individuals with cancer and studies on the immune response to HPV.
46 T H E N A T I O N A L C A N C E R I N S T I T U T E 

■ Support investigations into the role of co-carcinogenic agents (biological and chemical) in 

cancer initiation, promotion, and progression. Include investigations of the contribution of 

inflammation, injury, and specific mutations to lung carcinogenesis. 

■ Support investigations of the relationship between autoimmune diseases and the risk of cancer. 

■ Support studies to assess the effects of anti-inflammatory agents on cancers associated with 

microbial etiology. 

■ Continue to develop the vaccine program at NCI to target infectious agents that initiate and 

promote cancer. 

■ Support studies to identify and evaluate agents that will prevent or ameliorate cancer-causing 

radiological injury. 

1 dcb.nci.nih.gov/branchdetail.cfm?branch=1 

2 emice.nci.nih.gov 

3 home.ncifcrf.gov/mtdp 

4 dtp.nci.nih.gov/docs/rand/rand_index.html 

Integrative Cancer Biology 

Budget Increase Request for Fiscal Year 2006 

Developing computational models $24.00 M 

Integrative Cancer Biology Programs 

Training 

Mouse models for validation 

Innovative technologies for use in cells & animal models 

Bioprobes and candidates for drug development 

Understanding the tumor microenvironment 16.50 M 

Cross-disciplinary research alliance 

Training in using organotypic culture systems 

Studies on immune responses to cancer 

Resources for the development of small molecules & biologics 

Studying the tumor macroenvironment 24.00 M 

Collaborative research groups studying cancer viruses & microbial agents 

Studies of biological and chemical co-carcinogenic agents 

Studies of autoimmune diseases & cancer risk 

Effects of anti-inflammatory agents on cancer 

Vaccine development 

Studies to prevent/ameliorate radiological injury 

Management & Support 1.10 M 

Total $65.60 M
THE NATIONAL CANCER INSTITUTE 47 

Highly Lethal Cancers – Changing the Statistics 

In 2004, about 31,860 people in the United States will be diagnosed with pancreatic cancer. There will be about 

14,250 new cases of esophageal cancer, and an expected 18,920 people will be told they have liver cancer. 

These are highly lethal diseases. About 15 percent of Whites and 8 percent of African Americans diagnosed with 

esophageal cancer are expected to survive five years. The five-year survival rate for patients newly diagnosed 

with pancreatic cancer is estimated at just 4 percent. For liver cancer, it is 7 percent. If we are to reach our challenge 

goal to eliminate the suffering and death due to cancer, we must invest in research and development that will 

change these statistics. 

Epidemiologists have already identified several risk factors in common for these three cancers. For example, 

people who develop these cancers often have a history of chronic inflammation. Tobacco use, alcohol use, and 

obesity are also prevalent among people with these cancers. Large population studies are needed to draw valid 

statistical conclusions about the roles of genetic, environmental, and lifestyle factors in the initiation and 

progression of these diseases. 

One challenge is that the relative rarity and high lethality of pancreatic, esophageal, 

and liver cancers make it difficult to conduct these large studies. It is not unusual, 

for example, for population studies of breast or prostate cancer to enroll tens of 

thousands of participants. In contrast, the relatively low numbers of patients with 

highly lethal cancers demand significant cooperation and coordination to assemble 

enough patients to conduct even one study. NCI is proposing to address this 

obstacle by developing a consortium of investigators to conduct epidemiological 

studies of highly lethal cancers. 

This consortium approach will pool the resources of multiple institutions. Through 

the collection, storage, management, and sharing of data for a large numbers of 

cases, investigators will be able to amass enough knowledge to evaluate the 

possible combinations of genetic, environmental, and lifestyle factors – from 

molecular to behavioral – that are causing these cancers. This unparalleled collection 

of data will provide an ideal resource for exploring new hypotheses emerging from 

basic and clinical research, and provide hope for those individuals who suffer from 

highly lethal cancer.
48 THE NATIONAL CANCER INSTITUTE 

Strategic Investments in Molecular Epidemiology


Our Goal Understand the behavioral, environmental, genetic, and epigenetic causes of 

the vast majority of cancers in the human population in order to generate new means 

of prevention, detection, and treatment. 

Cancer is a complex disease that develops when the genes that regulate such functions as cell 

growth, cell death, and signal response are impaired. This impairment can occur through either 

genetic or epigenetic pathways. Genetic errors are caused by structural changes in the DNA of 

a person’s genes, whereas epigenetic transformation refers to those processes which cause normal 

cells to become tumor cells without the occurrence of any mutations affecting DNA or other 

genetic machinery. Some of these genetic and/or epigenetic errors are inherited. Others result 

from certain environmental exposures or individual behaviors such as energy balance status; 

tobacco and alcohol use; exposure to ionizing, solar, and other radiation; viruses and other 

infectious agents; imbalances in hormones and metabolic processes; and exposure to chemicals 

in the occupational and general environment. It is important to understand the roles of both 

inherited susceptibility and lifestyle or environmental risk factors for cancer. Furthermore, we 

need to uncover the interactions among genetic and environmental risk factors, harnessing 

the statistical power of bioinformatics and taking advantage of the emerging insights from 

integrative biology. 

NCI is developing novel ways to unravel the complexities of inherited and environmental 

contributions to cancer. We are supporting individual efforts as well as large collaborative 

programs to maximize the sharing of population data, biospecimens, laboratory models, and 

in vitro observations. In particular, large-scale studies with heightened levels of interdisciplinary 

cooperation and innovation are encouraged. Future 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 or mitigate adverse exposures. This expanded information will enable 

NCI to develop more effective approaches for the prediction, prevention, early detection, and 

treatment of cancer in all population groups. 

Expanding Our Understanding of Specific Cancers 

With increased resources in Fiscal Year 2006, we will expand efforts to understand specific 

types of cancer through consortia of cohort and case-control studies and consortia of cancer-prone 

families that integrate genomics, epigenomics, proteomics, and other emerging technologies into 

epidemiologic studies. We will: 

■ Initiate large-scale studies of highly lethal cancers (e.g., cancers of the pancreas, liver, and 

esophagus). 

■ Continue to conduct and analyze consortial studies of breast and prostate cancer and 

non-Hodgkin’s lymphoma and initiate consortial studies of ovarian and brain cancers. 

■ Expand existing international consortia for family-based studies (e.g., melanoma, leukemia, 

lymphoma, and testicular, colon, breast, prostate, and pancreatic cancers) and initiate familybased consortia for other cancers, in order to identify genetic determinants. 
THE NATIONAL CANCER INSTITUTE 49 

■ Expand the number of participants, population diversity, and types of biospecimens (including 

tumor specimens) in these consortia. 

■ Develop innovative review and reward processes that foster large-scale consortial research. 

Expanding Studies of Behavioral and Environmental Risk Factors 

We will also use new resources to expand studies on the influence of behavioral and environmental factors on the risk of cancer induction and progression, utilizing genetic and molecular 

probes, including studies in populations with exceptional or changing cancer rates or unusual 

environmental exposures. International studies and investigations of populations in transition, 

including migrant populations, provide particular opportunities for identifying biomarkers of 

carcinogenic exposure, genetic susceptibility, precursor states, and mechanisms of cancer causation. 

Special emphasis will be given to studies of specific behavioral factors (e.g., tobacco and alcohol 

use, energy balance) and their relation to cancer risk. In Fiscal Year 2006, we will: 

■ Fund and conduct etiologic studies targeted to U.S. minority groups, including Hispanic and 

African American populations. 

■ Initiate and fund studies of populations in transition, such as populations in Asia and migrant 

populations in the United States. 

■ Incorporate instruments to collect enhanced behavioral information on dietary and environmental exposures in case-control and cohort studies. 

■ Conduct population-based studies of cancer risk associated with tobacco and other products, 

including studies that explore molecular damage in former smokers. 

Integrating Population Science with Genomics and Other Technologies 

We are now in a position to greatly expand the knowledge base of cancer risk factors and 

biologic mechanisms through the convergence of epidemiologic and molecular approaches and 

the integration of population science with genomics and other emerging technologies. Research 

in this area has begun to yield important insights into a fundamental understanding of cancer 

causation, including the role of environmental and genetic determinants and their interactions. 

With sufficient resources in Fiscal Year 2006, we will establish a much needed, regional 

network of high-throughput laboratories for existing and emerging biomarkers of cancer risk. 

The network will provide the support for the genomic, molecular, and biochemical components 

of the molecular epidemiology consortia. We will: 

■ Build a network of high-throughput genotyping laboratories that incorporate advances in 

genomic technology into large-scale population studies. 

■ Initiate programs to implement public health measures and educational activities based on 

emerging genomic, epigenomic, and proteomic technologies. 
50 T H E N A T I O N A L C A N C E R I N S T I T U T E 

Molecular Epidemiology 

Budget Increase Request for Fiscal Year 2006 

Expanding understanding of specific cancers $35.25 M 

Large-scale studies of highly lethal cancers 

Disease-specific consortial studies 

International consortia for family studies 

Expansion and incentives for consortial research 

Expanding studies of risk factors 9.50 M 

U.S. minority groups 

Populations in transition 

Lifestyle & environmental exposures 

Integrating population science with emerging technologies 6.00 M 

Network of high-throughput genotyping laboratories 

Public health & education programs 

Partnering to leverage research resources 7.50 M 

Research on second primary cancers 

& recurrence 

Collaborative studies with the Gynecologic & 

Children’s Oncology Groups 

Supplemental funds to Cancer Centers 

Stimulating training & interdisciplinary research 1.40 M 

Joint training programs with medical & public 

health schools 

Interdisciplinary training & research awards 

Management & Support $1.02 M 

Total $60.67 M 

Partnering to Leverage Resources 

Partnerships with clinical oncology groups will allow us to leverage research resources and integrate 

clinical, laboratory, and population sciences. We will: 

■ Expand the program of surveillance and research into second primary cancers and recurrence 

to determine risk factors, such as the role of therapy and genetic susceptibility mechanisms, 

including DNA repair. 

■ Conduct collaborative studies of etiology and natural history with the Gynecologic Oncology 

and Children’s Oncology Groups conducting clinical trials. 

■ Provide supplemental funds to Cancer Centers to develop molecular epidemiology capabilities, 

especially for hospital-based case-control studies of highly lethal cancers. 

■ Develop population studies to identify 

genetic factors that affect tumor progression, prognosis, therapeutic outcomes, and 

side effects (e.g., pharmacogenomics). 

Stimulating Cross Training and 

Interdisciplinary Science 

Finally, initiatives to stimulate cross training 

and interdisciplinary and multidisciplinary 

research opportunities will provide a pool 

of investigators poised to advance the new 

and integrated objectives in molecular epidemiology. We will use new resources to: 

■ Work with medical and public health 

schools to develop joint training programs 

and new curricula in genetic and molecular epidemiology. 

■ Initiate new training awards for predoctoral students in interdisciplinary and 

multidisciplinary research relevant to 

molecular epidemiology. 

■ Initiate new interdisciplinary and multidisciplinary research awards in molecular epidemiology. 
THE NATIONAL CANCER INSTITUTE 51 

Strategic Partnerships Advance Studies in Molecular Epidemiology 

Epidemiology has been depicted as a scientific approach that moves slowly but with great force. By incorporating powerful new tools generated by recent advances in genomics and molecular sciences, however, 

we have an unparalleled opportunity to move more quickly and with greater impact than ever before. Poised 

to accelerate knowledge about the genetic and environmental components of cancer initiation and progression, 

our investments in Molecular Epidemiology will help identify new preventive, diagnostic, and therapeutic 

interventions. 

Cultivating strategic partnerships that link epidemiologists with one another and with genomicists and other 

investigators from the clinical, basic, and population sciences is integral to these investments. This transdisciplinary team-based approach responds to a growing consensus in the scientific community that the full 

potential of genomic and other emerging technologies will require large-scale epidemiologic studies. Study 

designs must have the efficiency and power to identify, from questionnaires and biospecimen collections, 

common low-penetrant susceptibility genes and their interactions with exogenous or endogenous exposures. 

This can be accomplished through consortia that combine the resources of several cohort and/or case-control 

studies in a coordinated approach that enables rapid replication of positive findings using independent 

datasets. This strategy avoids the cumbersome and expensive trial-and-error process that often occurs when 

false-positive findings from individual studies appear in the literature. When reproducible findings emerge in the 

consortia, pooling of datasets provides the statistical power to quantify the risks associated with specific 

gene variants and exposures and to enable subset analyses that uncover gene-gene and gene-environment 

interactions. 

One such partnership is the Consortium of Cohorts, an international collaboration of investigators responsible 

for 23 independently funded population cohorts involving 1.2 million individuals. Each cohort will characterize 

thousands of individuals who have developed cancer with extensive information on known or suspected risk 

factors and biospecimens (including germline DNA) collected prior to diagnosis. This consortium provides 

an integrative framework for nested case-control studies of specific cancers arising within the cohorts and 

opportunities to systematically evaluate molecular and biochemical biomarkers of susceptibility and earlystage disease. 

Other types of strategic partnerships are under development, including international case-control consortia of 

investigators responsible for population- or hospital-based studies of less common cancers that cannot be 

easily evaluated in cohort studies. In addition, several scientists interested in familial cancer have formed 

international family-based consortia. Current emphasis is on familial syndromes in which high penetrant genes 

have eluded discovery and on opportunities to identify genetic and environmental modifiers of inherited risk. 

Many complex scientific, administrative, and cultural challenges are involved in developing these team-based 

transdisciplinary partnerships, which seemingly run counter to the traditional model of individual investigators 

or groups that work independently. The two strategies are really complementary and synergistic, however, 

and they are speeding the discovery of causal agents and pathways, early detection markers, and interventions 

designed to prevent and control cancer. 
52 THE NATIONAL CANCER INSTITUTE 

Delivering the Promise 

NCI’s Budget Increase Request Emphasizes Patient Care and Public Health 

With a sizable portion of our increase request devoted to quality of care, survivorship, 

tobacco control, and energy balance issues, the seven strategic investment areas 

outlined in this document point to improved patient care and public health as our 

ultimate destination. 

Improving the Quality of Cancer Care 

Quality cancer care means evidence-based, patient centered care that is timely, technically 

competent, and administered with sound communication, shared decision making, and 

cultural sensitivity. NCI investments in Fiscal Year 2006 will support: 

■ Community-based interventions that address disparities in care and their potential to be 

replicated in a culturally appropriate manner. 

■ Training programs for creating a diverse and culturally sensitive research and care workforce. 

■ Collaborations to improve early detection, diagnosis, prognosis, treatment, and survivorship 

for people over 65. 

■ Collaborations for communicating risk, delivering evidence-based preventions, and evaluating 

prevention practices for improved patient outcomes. 

Optimizing Health and Quality of Life after Cancer 

For the nearly ten million Americans now living with a history of cancer, life after cancer means 

finding a new balance – one that celebrates the triumph and relief of completing treatment, 

recognizes changes or losses the disease has wrought, and assimilates revised perspectives, 

newfound strengths, and lingering uncertainties. NCI’s Fiscal Year 2006 investments will include 

research and development to: 

■ Better understand and address survivorship 

issues in underserved populations. 

■ Reduce the long-term side effects of cancer 

treatment and improve symptom management. 

■ Include more quality-of-life endpoints 

within NCI-supported clinical trials. 

■ Track, store, and retrieve patient information needed by healthcare providers for 

follow-up care. 

■ Identify genetic factors that affect prognosis, 

tumor progression, therapeutic outcomes, 

and side effects. 

Overcoming Cancer Health Disparities 

While Overcoming Cancer Health Disparities is one of our strategic investment areas for 2006, it is also emphasized in conjunction with other priorities. 

■ Prevention, Early Detection, and Prediction investments include tobacco 

research and dissemination in low- and middle-income nations, studies 

to project the impact of cancer interventions in specific populations, and 

identification of markers of cancer risk and cancer progression in high 

risk populations. 

■ Proposed Clinical Trials Integration efforts include increasing access to 

and participation of minority and underserved people in cancer clinical 

trials. 

■ Molecular Epidemiology efforts investments will expand the diversity of 

participants in consortia studies and support etiologic studies of minority 

groups and populations in transition.
THE NATIONAL CANCER INSTITUTE 53 

Understanding Tobacco Use and Tobacco-Related Cancers 

Tobacco use is the leading preventable cause of illness and death in the United States. Cancers 

of the lung, oral cavity, pharynx, larynx, esophagus, pancreas, urinary bladder and renal pelvis 

have all been scientifically linked to tobacco use. Dramatically reducing and treating tobacco 

use and tobacco-related cancers across all ages and populations is critical to eliminating the 

suffering and death due to cancer. NCI investments in Fiscal 2006 will support: 

■ Tobacco use prevention and smoking cessation research that addresses underserved and 

understudied youth and young adults. 

■ Health behaviors research, including tobacco use, among medically underserved people who 

have survived cancer. 

■ A tobacco and health disparities research network. 

■ Research on effective State and community programmatic and policy interventions for 

tobacco control. 

■ International research on tobacco control, prevention, and dissemination to benefit low- and 

middle-income nations. 

■ Determination of the cancer risk potential of reduced-exposure tobacco products. 

■ Studies to identify cellular targets and screen and develop agents to help smokers quit and 

prevent cancers in former smokers. 

■ Population-based studies of cancer risk associated with tobacco, including molecular damage 

in former smokers. 

■ Large-scale studies of highly lethal cancers, several of which are tobacco related. 

■ A National Lung Screening Trial Image Library to optimize diagnostic programs. 

Understanding and Promoting Energy Balance to Prevent Cancer 

Compelling evidence suggests that excess body weight is a risk factor for many cancers. Body 

weight is determined by each individual’s “energy balance,” the complex interaction among 

diet, physical activity, and genetics over his or her lifetime. NCI’s research goals include 

understanding the causes of adverse patterns of weight, physical activity, and diet; defining 

how these causes contribute to cancer; and applying this knowledge to prevent and control 

cancer. NCI investments in Fiscal Year 2006 will support: 

■ Multidisciplinary research on patterns of diet and exercise among cancer survivors and in 

underserved populations. 

■ Development of innovative approaches for prevention of obesity. 

■ Studies to identify the molecular mechanisms of bioactive food components as modifiers of 

cancer risk and tumor behavior. 

■ Studies to evaluate physiological changes influenced by dietary components in normal and 

cancerous processes. 

■ Development of new technologies for assessing energy intake and balance. 

■ Collection of behavioral information on dietary and environmental exposures in case-control 

and cohort population studies.
What we learn through continued studies in Molecular Epidemiology and Integrative Cancer 

Biology coupled with Advanced Technologies in bioinformatics, imaging, proteomics, and 

nanotechnology will provide the knowledge and tools to link research progress across all areas 

of strategic investment. 

Cancer Initiation 

Overcoming Cancer Health Disparities is essential at every juncture from 

basic discovery to intervention development to the collaborative delivery of 

public health programs and patient care. 

At a Glance 

Metastatic Progression 

An Integrated Clinical Trials System will streamline processes and speed delivery of new preventive agents, diagnostic 

approaches, and cancer treatments to all who need them. 

Malignant Transformation 

Strategic Development of Cancer Interventions will increase our 

capacity for delivering molecularly based diagnostics and treatment. 

Susceptibility & Pre-Cancerous Changes 

Prevention, Early Detection, and Prediction initiatives will provide needed resources 

for making prevention our first line of defense against cancer and improving our ability 

to detect, diagnose, and treat cancer at its earliest stages. 

T H E N A T I O N A L C A N C E R I N S T I T U T E 

Our Strategic Investments Will Help Preempt Cancer at Every Stage 

NCI’s Budget Request for Fiscal Year 2006 (dollars in thousands) 

Fiscal Year 2005 Congressional Justification Budget $4,870,025 

Core Budget Increases 609,785 

(includes funding of RPGs, limited expansion 

of Cancer Centers and SPOREs, construction, 

maintenance, and personnel) 

Strategic Investment Increases 

Cancer Prevention, Early Detection, and Prediction 112,120 

Overcoming Cancer Health Disparities 39,150 

Strategic Development of Cancer Interventions 119,000 

An Integrated Clinical Trials System 170,850 

Advanced Technologies 122,800 

Integrative Cancer Biology 65,600 

Molecular Epidemiology 60,670 

Subtotal Strategic Investment Increases 690,190 

Total Fiscal Year 2006 Budget Request* $6,170,000 

* In addition, a National Advanced Technology Initiative for cancer (NATIc) is described 

on pages 40-41, including the initiative's resource requirements.
T H E N A T I O N A L C A N C E R I N S T I T U T E 

The Nation's Investment in Cancer Research 

Distribution of Fiscal Year 2006 Budget Request ($6,170,000,000) 

Research Project Grants 48.3% 

Intramural Research 12.6% 

Cancer Centers 10.5% 

Clinical Trials Infrastructure 5.4% 

Training and Education Grants 3.5% 

Cancer Control Operations 2.7% 

Research Support Contracts 12.1% 

Research Management and Support 3.3% 

Other Grants 1.0% 

Construction 0.4% 

Repairs and Improvements 

at NCI-Frederick 0.2% 

Distribution of Fiscal Year 2006 Requested Increases ($1,299,975,000) 

Research Project Grants 51.9% 

Intramural Research 4.0% 

Cancer Centers 12.6% 

Clinical Trials Infrastructure 5.4% 

Training and Education Grants 2.1% 

Cancer Control Operations 0.7% 

Research Support Contracts 18.9% 

Research Management and Support 1.8% 

Other Grants 0.2% 

Construction 1.9% 

Repairs and Improvements 

at NCI-Frederick 0.5% 

Research Project Grants 

Funding for extramural research, primarily 

through Research Project Grants (RPGs), 

comprises the largest part of the NCI core 

budget. We fund about 4,500 RPGs each year 

to nearly 600 institutions across the United 

States at an average cost of approximately 

$400,000 per grant. 

Intramural Research 

NCI intramural research focuses on projects 

conducted by some 400 researchers located on 

the NIH campus. Some of these investigators 

conduct long-term epidemiologic and genetics 

studies requiring the continuity of an intramural program. Others work synergistically 

with other NIH Institutes and with the NIH 

Clinical Center to quickly transfer laboratory 

research to the clinic. 

Cancer Centers and Specialized 

Programs of Research Excellence 

(SPOREs) 

Some 60 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. 
54 T H E N A T I O N A L C A N C E R I N S T I T U T E 

National Cancer Institute 

Budget Request for Fiscal Year 2006 

(dollars in thousands) 

2004 

Operating 

Budget 

2005 

Congressional 

Justification 

2006 Budget Request 

2006 

Increases 

2006 

Budget 

Request 

Research Project Grants (RPGs) 

Ongoing $1,663,656 $1,701,664 $93,818 $1,795,482 

New and Renewal 492,369 501,682 554,163 1,055,845 

Subtotal RPGs 2,156,025 2,203,346 647,981 2,851,327 

Small Business Innovation Research (SBIR) 99,979 103,773 26,632 130,405 

Total RPGs 2,256,004 2,307,119 674,613 2,981,732 

Intramural Research 687,193 725,344 51,462 776,806 

Cancer Centers 

Comprehensive/Clinical/Basic (P30) 
 250,022 244,710 69,564 314,274 

Planning Grants 
 0 10,815 379 11,194 

Specialized Center (U54) 
 26,088 46,272 40,120 86,392 

Specialized Programs of Research Excellence (SPOREs) 
 185,387 178,902 54,262 233,164 

Subtotal Cancer Centers 461,497 480,699 164,325 645,024 

Clinical Trials Infrastructure 

Cooperative Clinical Research 153,882 167,330 36,957 204,287 

Community Clinical Oncology Program (CCOPs) 95,424 98,118 32,934 131,052 

Subtotal Clinical Trials Infrastructure 249,306 265,448 69,891 335,339 

Training and Education Grants 

National Research Service Awards 66,480 
 70,860 8,480 79,340 

Research Career Program 75,346 
 76,812 12,888 89,700 

Cancer Education Program 31,769 
 32,006 5,120 37,126 

Minority Biomedical Research Support 4,012 
 7,890 477 8,367 

Subtotal Training and Education Grants 177,607 187,568 26,965 214,533 

Cancer Control Operations 143,930 157,596 9,390 166,986 

Research Support Contracts 538,607 504,335 245,152 749,487 

Research Management and Support 165,581 177,224 23,993 201,217 

Other Research Grants 52,473 56,692 2,184 58,876 

Construction 25,000 25,000 

Repairs and Improvements at NCI-Frederick 8,000 7,000 15,000 

Total Budget Request 4,732,198 4,870,025 1,299,975 6,170,000 

Cancer Control included above* 521,487 544,890 135,776 680,666 

Clinical Trials Infrastructure 

NCI supports clinical trials at the NIH clinical 

center and at close to 3,000 other sites across 

the U.S. 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. 

Training and Education Grants 

NCI funds training and education programs 

involving approximately 170 institutions and 

2,000 individuals each year to prepare the 

next generation of scientists and clinicians to 

use new technologies and to work effectively 

in interdisciplinary, collaborative research 

environments. Increased funding will be 

used to support the development of interdisciplinary team science and to increase 

the number of scientists working with 

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 information dissemination activities. 
THE NATIONAL CANCER INSTITUTE 5 5

Research Support Contracts

Research support contracts are used for

diverse programs across the Institute. These

include drug development, cancer control

research, information dissemination, and 

support to epidemiological research.

Research Management and Support

Research management and support funds 

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

out its work. They cover the cost of central

administrative functions, overall program

direction, grant and contract review 

and administration, personnel, program 

coordination, and financial management.

Other Grants

Other grants support partnerships; shared

resources; and scientific evaluation, 

workshops, and conferences.

Requested Increases for Fiscal Year 2006

Strategic 

(dollars in thousands) Core** Investments Total 

Research Project Grants (RPGs) 

Ongoing $90,318 $3,500 $93,818 

New and Renewal 263,013 291,150 554,163 

Subtotal RPGs 353,331 294,650 647,981 

Small Business Innovation Research (SBIR) 26,632 26,632 

Total RPGs 379,963 294,650 674,613 

Intramural Research 35,387 16,075 51,462 

Cancer Centers 

Basic/Clinical/Comprehensive (P30) 63,564 6,000 69,564 

Planning Grants 379 379 

Specialized Center (U54) 1,620 38,500 40,120 

Specialized Programs of Research Excellence (SPOREs) 38,262 16,000 54,262 

Subtotal Cancer 103,825 60,500 164,325

Centers

Clinical Trials Infrastructure 

Cooperative Clinical Research 5,857 31,100 36,957 

Community Clinical Oncology Program (CCOPs) 3,434 29,500 32,934 

Subtotal Clinical 9,291 60,600 69,891 

Trials Infrastructure 

Training and Education Grants 

National Research Service Awards 2,480 6,000 8,480 

Research Career Program 7,688 5,200 12,888 

Cancer Education Program 1,120 4,000 5,120 

Minority Biomedical Research Support 477 477 

Subtotal Training and 11,765 15,200 26,965 

Education Grants 

Cancer Control Operations 5,515 3,875 9,390 

Research Support Contracts 17,652 227,500 245,152 

Research Management and Support 12,203 11,790 23,993 

Other Research Grants 2,184 2,184 

Construction 25,000 25,000 

Repairs and Improvements at NCI-Frederick 7,000 7,000 

Total Increase Request 609,785 690,190 1,299,975 

** Core funds will be used for maintaining the FY 2005 program level of

effort; funding 35% of competing RPGs at recommended levels and

funding non-competing RPGs at committed levels; limited expansion for

Cancer Centers, SPOREs, the Research Career Program, Construction,

and Repairs and Improvements at NCI-Frederick; and funds for an 

additional 100 full-time-equivalent staff members. 
56 T H E N A T I O N A L C A N C E R I N S T I T U T E 

Acknowledgments 

The NCI Office of Science Planning and Assessment (OSPA) 


provides leadership and guidance for plan development from 


conceptualization to production. OSPA staff work alongside 


NCI leaders and the Office of Budget and Financial Management


for plan and budget development and with the Office of


Communications for document production and distribution. 


This year, the OSPA team was led by Cherie Nichols and 


Kathie Reed and included Marianne Kost, Kathy Sorrow,


Kate McNeill, Kevin Callahan, Anna Levy, Samir Sauma,


Margaret Ames, Lisa Stevens, and Anne Tatem. Others in the


office who provided support to the effort were Buddy Clark,


Norma Davis, Camille Haylock, D. J. Joya, Christine Moretto,


and Clara Sliva.


The following NCI teams worked together to identify 2006 


activities for the various Strategic Investment areas. 


Molecular Epidemiology: Joe Fraumeni, Bob Hoover, 


Grace Ault, Neil Caporaso, Steve Chanock, Ken Chu, 


Paulette Gray, Patricia Hartge, Carol MacLeod, Catherine


McClave, Sandra Melnick, Arthur Schatzkin, and Ed Trapido


Integrative Cancer Biology: Dinah Singer, Rachel Ballard-Barbash,


Dan Gallahan, Jim Jacobson, Jill Johnson, Carol Kasten-Sportes,


Gary Kelloff, Kathy Kelly, Michael Leitzmann, Cheryl Marks,


Susan McCarthy, Jim McMahon, Anne Menkens, Suresh Mohla,


John Sogn, Barbara Spalholz, Vernon Steele, and May Wong


Prevention, Early Detection, and Prediction: Peter Greenwald,


Bob Croyle, Kara Smigel-Croker, Stacey Vandor, Roger Aamodt,


Nelvis Castro, Jim Crowell, Rocky Feuer, Andrew Freedman,


Richard Hayes, Lee Helman, Allan Hildesheim, Scott Leischow,


Ed Maibach, Helen Meissner, John Milner, Howard Parnes,


Sudhir Srivastava, Dan Sullivan, Emmanuel Taylor, and 


Ed Trapido


Strategic Development of Cancer Interventions: Ann Barker, 


Greg Downing, Cathy Backinger, Martin Brown, 


Michaele Christian, Norm Coleman, Jennifer Couch, 


Frank Govern, Kevin Howcroft, Gary Kelloff, Ed Maibach,


Robert Mufson, Linda Nebeling, and John Sogn


Integrated Clinical Trials System: Jim Doroshow, 


Howard Fine, Jeff Abrams, Karen Antman, Michelle Bennett,


Michaele Christian, Roland Garcia, Louise Grochow, 


Lenora Johnson, Lori Minasian, Glen Morgan, Ann O’Mara, 


Julia Rowland, Anne Ryan, Lalitha Shankar, Mike Stefanek, 


and Linda Weiss


Overcoming Cancer Health Disparities: Harold Freeman, 


Michelle Bennett, Linda Brown, Gail Bryant, John Cole, 


Jane Daye, Susan Devesa, Pebbles Fagan, Frank Govern, 


Suzanne Heurtin-Roberts, Steve Hursting, 


Diana Jeffery, Brian Johnson, Jon Kerner, Dee Lawrence, 


Worta McCaskill-Stevens, Vickie Shavers, Sanya Springfield,


Manuel Torres-Anjel, Linda Weiss, Debbie Winn, 


Nada Vydelingum, and Jo Anne Zujewski 


Advanced Technologies: Ken Buetow, Greg Downing, 


Dan Sullivan, Andrew Bergen, Brenda Edwards, Howard Fine,


Dan Gallahan, Carl Jaffe, Randy Knowlton, Marsha Reichman,


Daniela Seminara, Jeff Shilling, and Barbara Wingrove


A special thank you also goes to Jim Dickens, Karen Colbert, 


Ann Fitzpatrick, and Ngan Nguyen in the Office of Budget 


and Financial Management, to Nelvis Castro, Donna Bonner, 


Julie Cheh, Diane Reid, and Paul LaMasters in the Office of


Communications, and to Mark Clanton, John Hartinger, 


Dotty Foellmer, Carl Barrett, Kathleen Schlom, Elisabeth Handley,


John Hoffman, Linda Anderson, James Tatum, Jeffrey Schlom,


and Doug Lowy for their encouragement and support in the 


development of this document. 


Lynne Komai, Don Wheeler, and Claudia Smith of The


Watermark Design Office provided design support and 


Walt Burroughs provided guidance to the printing process.


We thank the following individuals and organizations for writing to 

us in response to our call for input in the spring of 2004: Grover 

C. Bagby, Tomasz Beer, Bill Blair, Susan Braun, Margaret Cary, 

Leslie Cyril, Ralph W. de Vere White, Eric Dishman, Ann Fonfa, 

Ralph S. Freedman, Eugene W. Gerner, Dennis L. Gibson, Arny 

Glazier, Russ Gould, Dorothy K. Hatsukami, Malcolm Hendry , 

Barbara B. Knowles, William H. Kramer, Chung Lee, Barbara 

LeStage, Isaac Lipkus, Jeannie Lovastik, Charles C. Maack, 

Jamie McDonald, Susan Nathanson, C. Kent Osborne, Julie P. 

Pawelczyk, John C. Reed, Carole Seigel, Katherine Loy Stadler, 

Rem Stokes, Joel Tepper, Tim Thompson, Kristiina Vuori, Susan 

L. Weiner, Jean A. Wooldridge, Rick Woychik, Kathleen Zeitz, the 

American Society for Therapeutic Radiology and Oncology, the 

Arizona Cancer Center and Specialized Program of Research 

Excellence, Baylor College of Medicine, Bone Cancer 

International, Drug Innovation and Design Inc., Duke University, 

the Fred Hutchinson Cancer Research Center, Hoag Memorial 

Hospital, Intel Proactive Health Research, the M. D. Anderson 

Cancer Center, National Breast Cancer Awareness Month, 

Northwestern University, the Oregon Health & Science University 

Cancer Institute, the Pancreatic Cancer Action Network, 

Presbyterian Healthcare Services, the Susan G. Komen Breast 

Cancer Foundation, The Annie Appleseed Project, The Burnham 

Institute and Cancer Center, The Children’s Cause, The Jackson 

Laboratory, University of California Davis Cancer Center, 

University of Minnesota Transdisciplinary Tobacco Use Research 

Center, Us TOO-Kansas, and Us TOO-Texas. 
Valuable World Wide Web Locations


For Cancer Information 

National Cancer Institute cancer.gov 

NCI Cancer Information Service cis.nci.nih.gov 

Cancer News newscenter.cancer.gov 

Cancer Science newscenter.cancer.gov/sciencebehind 

Progress Report progressreport.cancer.gov 

Mortality Maps and Graphs www.cancer.gov/atlasplus 

Surveillance, Epidemiology, and End Results seer.cancer.gov 

NCI Annual Report cancer.gov/aboutnci/annualreport 

National Institutes of Health www.nih.gov 

Department of Health and Human Services www.hhs.gov 

Planning and Priority Setting at NCI 

This Document Online plan.cancer.gov 

Office of Science Planning and Assessment planning.cancer.gov 

Disease-Specific Research Agendas prg.cancer.gov 

Disease-Specific Research Initiatives cri.cancer.gov 

Information Related to the Contents of this Document (all accessible from cancer.gov) 

Cancer Research and Development Portfolio 

NCI Portfolio researchportfolio.cancer.gov 

International Portfolio www.cancerportfolio.org 

Clinical Trials cancer.gov/clinicaltrials 

NCI Research and Development Tools 

Research Resources resresources.nci.nih.gov 

Cancer Genome Anatomy Project cgap.nci.nih.gov 

Center for Bioinformatics ncicb.nci.nih.gov 

Cancer Imaging Programs cancer.gov/bip and 

ccr.cancer.gov/tci/imaging.asp 

Developmental Therapeutics Program dtp.nci.nih.gov 

Intramural Resources ccr.cancer.gov/initiatives 

Nanotechnology nano.cancer.gov 

Technology and Industrial Relations otir.cancer.gov 

Cancer Research Funding 

Funding Opportunities cancer.gov/researchfunding 

Initiatives by Type of Research cri.cancer.gov 

Contacting the NCI Cancer Information Service 

By phone 

1-800-4-CANCER (1-800-422-6237) 

For deaf and hard-of-hearing 1-800-332-8615 

This service includes telephone-based assistance 

for smokers who want to quit. 

On the Web 

cis.nci.nih.gov 

Centers, Networks, and Consortia 

NCI Cancer Centers Program cancer.gov/cancercenters 

Specialized Programs of Research Excellence spores.nci.nih.gov 

Early Detection Research Network 

cancer.gov/prevention/cbrg/edrn 

Cancer Family Registries epi.grants.cancer.gov/CFR 

Cancer Genetics Network epi.grants.cancer.gov/CGN 

Mouse Models of Human Cancers Consortium emice.nci.nih.gov 

Training Opportunities 

Research Training, Career Development, and Education cancertraining.nci.nih.gov 

Cancer and Public Health 

Health Disparities crchd.nci.nih.gov 

Survivorship Research dccps.cancer.gov/ocs 

Tobacco Research dccps.cancer.gov/tcrb 

Quality of Care appliedresearch.cancer.gov 

Health Communications dccps.cancer.gov/hcirb 

Ordering this Document 

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 
NIH Publication No. 05-5612 

December 2004 

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.