The National Cancer Institute

The Nation’s

Investment in

Cancer Research

A Plan and Budget Proposal

for Fiscal Year 2003

P re p a r ed by the Dir e c t o r

National Cancer Institute 

National Institutes of Health

A Plan and Budget Proposal

for Fiscal Year 2003
. . . bringing together the resources to stimulate and support scientific discovery and its

application to achieve a future when all cancers are uncommon and easily treated.

Each year our work involves the efforts of a multitude of dedicated people across the United States

and around the world. 

■ Almost 5,000 principal investigators lead

research projects to understand cancer and

develop better ways to prevent, detect, treat,

and control it. These people conduct studies at

NCI and at nearly 650 universities, hospitals,

and other sites in our country and abroad.

■ More than 10,000 physicians and 200,000

patients participate in NCI-sponsored clinical

trials for cancer treatment, prevention, and early

detection interventions. About 1,300 trials will

be conducted in 2001 at 1,700 hospitals and

cancer centers around the country.

■ Thousands of scientific, health care, technical,

and other specialists carry out the vital day-today laboratory, clinical, and administrative work

of cancer research. 

■ Nearly 2,000 students and postdoctoral fellows

pursue the specialized research training required

to become part of the next generation of cancer

scientists and research leaders. 

■ Hundreds of scientific and medical experts and

representatives of advocacy groups help NCI

identify research needs and opportunities, set

priorities, and assess progress. 

The National Cancer Institute
T

he National Cancer Institute is a remarkable

enterprise that represents a unique confluence

of history, politics, science, technology, and

even philosophy. It is a public institution dedicated

to reducing the burden of cancer for all our Nation’s

citizens and people around the world. Through basic

intellectual inquiry, the generation of new knowledge

and tools, and the application of discovery, it has the

capacity to change the course of history by reducing

the terrible toll placed on people and society by that

group of diseases we call cancer. NCI is successful

because we are part of an extensive network of biomedical and broad scientific research and technology

that gives us the tools to ask questions, find and

interpret answers, and turn those answers into useful

ways of enhancing health and reducing disease. 

Each year, my colleagues and I prepare this plan

and budget proposal, as prescribed by the National

Cancer Act of 1971. To set forth new goals and

objectives for the “Nation’s investment in cancer

research,” we first examine the gaps in our understanding of cancer and our ability to translate and

apply what we know for the benefit of people. This

analysis helps us determine the larger context in

which we carry out our mission. 

The primary gap upon which all of our efforts are

predicated is the one between ignorance and knowledge about this disease. Attempting to address the

many unanswered questions about cancer is an

incredibly challenging intellectual exercise and an

essential step in successfully and predictably reducing its burden. Increasing our knowledge about cancer is difficult, complex, and often confusing. The

road to discovery often takes us in unexpected directions and brings us to unexpected outcomes or

insights. We must explore blind alleys, question and

change old knowledge and beliefs, and figure out

how seemingly unrelated pieces of information fit

t o g e t h e r. Working as part of a community, we constantly draw on new talent, evolve and use new

tools, and capitalize on creativity, intelligence, persistence — and very often, luck!

Our second task is to close the gap between knowledge gained through science and the translation of

that information to the actual experience of people at

risk for, diagnosed with, or surviving cancer. This

requires moving new knowledge directly into the setting of the disease. We must establish new insights

into individual risks for developing cancer; new, more

targeted approaches to early detection; a new molecular view of diagnosis; and entirely new approaches to

the prevention, treatment, and control of cancer and

its consequences. This type of translational research

is our first step in the transformation of cancer medicine and public health to more certainty and precision. It is our road to transforming therapy from trial

and error to rational design and the development of

targeted interventions. 

Third, our NCI activities must address the gap

between this translational work and actually reducing

the burden of cancer between what m i g h t w o r k o r

looks pro m i s i n g and what really d o e s work. We need to

move research results to their application in clinical

practice and public health by conducting extensive

clinical trials that will define the details of how new

approaches will work and determine what the benefits and risks of specific interventions are. This clinical research establishes or refutes the extent of benefit to patients of new approaches to reducing the risk

of, preventing, detecting, diagnosing, and treating

cancer — and provides the bridge to better, less invasive, and longer-term solutions. 

The final gap that we strive to close is one of the

most frustrating because it seems to be due to things

that we should have the power to influence and

change. This is the discontinuity between what we

Director’s Message 1

D i r e c t o r ’s 

M e s s a g e
2 The Nation’s Investment in Cancer Research

have already established as effective in reducing the

burden of cancer and the practice and availability of

that hard-won knowledge for a l l people regardless of

where they live, whether they are rich or poor, or

what their cultural backgrounds are. Bridging this

divide requires better understanding the unequal burden of this disease, addressing disparities in the quality of cancer care, and implementing the most effective interventions to address them. 

We must work to bridge each of these gaps

through the dissemination, diffusion, and adoption of

new insights. This means finding the most effective

ways to share findings and encourage collaborations

among researchers. It means applying the best communications technologies to facilitate translational

and clinical trial activities. And it means arming

practitioners with the information and tools they

need to achieve a level of comfort that will allow

them to successfully use new approaches in their work

with cancer patients, people at risk, and survivors. 

The true measure of excellence for an enterprise is

both where it can go and where it has been. With our

future planning, we look back to the myriad of initiatives supported by NCI and how these have begun to

close the gaps, and we look ahead to the many important next steps needed to continue. As stewards of

the public trust, we have a grave responsibility to

chart a course and develop a plan and budget that will

allow us to maintain the superior quality of all of our

research programs. In addition, we must meet the

challenges that come with new approaches, technolo g y, and knowledge and build on past discovery in

areas of “extraordinary opportunity” that address all

cancers as well as the specific needs of different types

of cancer. And through all of these efforts, we must

remain vigilant in addressing the barriers to full

implementation of new interventions that will bring

quality cancer care to a l l p e o p l e .

Our plans emerge through the insights and wisdom

we gain from the input, questioning, feedback, and

collective experience of all involved in the cancer

research enterprise. The future plans and priorities we

identify now set the rationale for our decisions along

the way, give us a systematic framework for assessing

progress, and provide a clear and credible means for

reporting our performance and results to the public. 

But these plans, these strategies, these technologies provide only a framework. The real work begins

with people, people who are at the heart of delivering

the full promise of our plans and investments. These

people, be they patient or health care provider, scientist or administrator, advocate or lawmaker are the

ones we must count on to close the gaps between

ignorance and knowledge, knowledge and application, and burden and access to or availability of care. 

Though the focus and methods have changed as

the science has evolved, our goal to improve the

plight of all people everywhere is unwavering. Wi t h

the courage of our cancer research and care community and the continued strength of our resources,

hope is stronger and more certain than ever, and the

years to come hold promise beyond our imaginations! 

Richard D. Klausner, M.D. 

D i r e c t o r

National Cancer Institute

September 2001
Director’s Message .......................................................................................................................1

Executive Summary .....................................................................................................................4

Highlights of Progress .................................................................................................................9

Our Role in Cancer Research ....................................................................................................14

2003 Budget Request ..................................................................................................................18

NCI’s Challenge: Building Our Capacity for the Future ........................................................20

Enhancing Investigator-Initiated Research .............................................................................21

Centers, Networks, and Consortia ...........................................................................................25

National Clinical Trials Program..............................................................................................29

Studying Emerging Trends in Cancer.......................................................................................35

Quality of Cancer Care ............................................................................................................40

Reducing Cancer-Related Health Disparities ..........................................................................45

Informatics and Information Flow............................................................................................50

Cancer Research Training and Career Development .............................................................54

Extraordinary Opportunities for Investment ............................................................................60

Genes and the Environment.....................................................................................................61

Cancer Imaging.........................................................................................................................66

Defining the Signatures of Cancer Cells..................................................................................71

Molecular Targets of Prevention and Treatment.....................................................................78

Research on Tobacco and Tobacco-Related Cancers...............................................................83

Cancer Communications..........................................................................................................88

Planning National Agendas in Disease-Specific Research .......................................................93

30 Years Later 

Hope and Promise Are Becoming Real....................................................................................98

How It All Comes Together.....................................................................................................99

A Story of Discovery

Making the Connections for a Targeted Cancer Treatment Takes Time and Perseverance...76

Spotlights on Research

Results Show Value of SPOREs................................................................................................28

SEER Increases Coverage and Forms Partnerships ..................................................................38

CGAP Is a Gateway to New Exploration and Discovery........................................................52

Modeling Human Cancers in the Mouse.................................................................................58

Table of Contents 3

Table of 

C o n t e n t s
E x e c u t i v e

S u m m a r y

T

he National Cancer Institute’s goal is to stimulate

and support scientific discovery and its application to achieve a future when all cancers are

uncommon and easily treated. NCI works toward

this goal in two major ways. We provide vision to the

Nation and leadership for NCI-funded researchers

across the United States and around the world, and

we work to ensure that the results of research are used

in clinical practice and public health programs to

reduce the burden of cancer for all people. 

Each year, we support some 5,000 principal

investigators in the pursuit of a broad range of

research from studies of the causes and incidence of

cancer to translational research and clinical trials to

survivorship and end-of-life issues. NCI also funds

cancer centers; collaborative research teams; cancer

control; and training, education, and career development activities. 

Our future planning encompasses three key components required for a strong cancer research enterprise. These are to maintain a sound research infrastructure and build capacity for the future (NCI’s

Challenge), to capitalize on opportunities in broad

scientific areas (Extraordinary Opportunities for

Investment), and to assess and plan for research related to specific types of cancer such as breast or lymphoma (Planning National Agendas for DiseaseSpecific Research). 

Our total Fiscal Year 2003 Budget Request is

$5,690,000,000. This represents an increase of

$1,512,796,000 over the Fiscal Year 2002 President’s

Budget. Of this increase, $305,753,000 will be provided to continue NCI commitments into 2003 (Core

Budget). An additional $878,193,000 will be used for

N C I ’s Challenge, and $328,850,000 will support

Extraordinary Opportunities for Investment. Funding

for disease-specific research is included in nearly all of

the Challenge and Opportunity areas. 

NCI’S CHALLENGE

M

ajor breakthroughs depend on building and 

sustaining the strong research mechanisms, 

support structures, and collaborations that will enable

us to pursue rapidly evolving discoveries in all areas of

cancer research. NCI must provide the vision, 

creative environments, and diverse resources needed

to ensure a smooth flow between advances in knowledge and their application.

Enhancing Investigator-Initiated Research

I n v e s t i g a t o r-initiated research has always been the

driving force behind advances in biomedical

research. Our challenge is to provide scientists with

opportunities to pursue as many promising research

ideas as possible while at the same time supporting

each project with sufficient funds to cover the 

growing costs of research. NCI gives special consideration to proposals from clinical researchers and

those who respond to announcements of priority

research areas. We seek to maximize the pace of discovery by providing a broad range of flexible funding

options and promoting collaborations and resource

sharing. With increased funding in 2003, we will be

able to support research projects at the full levels 

recommended by peer reviewers and fund the top 35

percent of competing grant applications. We will

continue to allocate the first 80 to 90 percent of

available funds for research project grants through

conventional selection processes while ensuring that

proposals from new investigators are also funded and

that exceptions funding is available to support particularly innovative and potentially high reward projects. 

4 The Nation’s Investment in Cancer Research
Centers, Networks, and Consortia

The rapid pace of scientific and technological discovery is creating opportunities that require interaction

among scientists of diverse backgrounds sometimes

located in physically distant sites. The challenge for

NCI is to create research settings that encourage the

multidisciplinary collaborations needed to address

the big picture problems in cancer research. To meet

this challenge, we continue to support NCI-designated Cancer Centers, Centers of Research Excellence,

and various research networks and consortia that

enable scientists from different disciplines to work

t o g e t h e r, share information and resources, and experience the synergism that often catalyzes new discovery.

In 2003, NCI will use new funding to increase support to Cancer Centers for new technology development, improved informatics capabilities, and clinical

and population research infrastructure; expand and

enhance the Specialized Programs of Research

Excellence based on needs for disease-specific

research; and implement a Strategic Supplement

Program to take advantage of high priority opportunities that can be completed in short time frames. 

National Clinical Trials Program in

Treatment and Prevention

Our intricate clinical trials system relies on cooperation and collaboration among patients, investigators,

i n d u s t r y, academia, and NCI. Adding to this comp l e x i t y, cancer clinical trials have undergone dramatic

changes in recent years, the result of progress in cancer biology, imaging technology, and advances in

informatics and electronic communications generating both the need and the possibility for more trials

involving much larger numbers of health care

providers and patients. While NCI-supported clinical

trials have incorporated many changes, reimbursement to health care providers has not kept pace and

participation in clinical trials remains lower than

ideal. Our challenge is to minimize the barriers to

participation in clinical trials while ensuring that we

capitalize on the latest developments in cancer

research, informatics, and management. With adequate funding in 2003, NCI will be able to improve

patient access to and the rate at which trials are completed by increasing the per patient reimbursement for

trials, doubling the number of patients accrued to trials,

providing follow-up funding for healthcare providers to

follow patients and report outcome and other data, and

expanding the Clinical Trials Support Unit. We also

will be able to expand funds for clinical correlative

studies; fund tissue and specimen banks; create collaborations for multi-institutional clinical trials; and step

up development and assessment of promising targeted

prevention and treatment agents. 

Studying Emerging Trends in Cancer

NCI must continue to build a versatile cancer surv e i l l a n c e system that fully represents the diversity of

our nation’s population and more accurately tracks the

N a t i o n ’s cancer burden. This information is needed t o

help researchers form hypotheses and to provide communities with the information they need to strengthen

cancer prevention and control. NCI works with partners to develop a more robust system, create analytical tools for research and cancer control, and find

effective ways to disseminate surveillance information. In 2003, we will use additional funding to augment and refine our surveillance system to keep pa c e

with a rapidly changing cultural, social, and technological milieu and continue to build systems that better

track cancer trends, highlight research needs, explain

causes of cancers, identify individuals at greatest r i s k ,

and support community cancer control. 

Quality of Cancer Care

The quality of cancer care is a major national concern.

Evidence suggests that some patients with cancer do

not receive the newer, more effective treatments, and

there is often uncertainty about what constitutes optimal care. To address these concerns, NCI is helping

to enhance the information base for cancer care decision making through improvements in data collection

and the development of better measures for comparing cancer treatments and outcomes. Furthermore, we

are also investing in studies to examine the quality of

cancer care and in demonstration projects to ensure

that the delivery of care reflects the latest findings from

cancer research. With funding increases in 2003, NCI

will engage in activities to improve measurement of

patient-centered outcomes in cancer; support innovative research on the diffusion, quality, and outcomes of

cancer interventions; and enhance quality-of-care

research within the NCI clinical trials program. 

Reducing Cancer-Related Health

Disparities

To effectively reduce cancer-related health disparities,

NCI must make new research investments to explain

social, cultural, environmental, biological, and behavExecutive Summary 5
ioral determinants of cancer, the interactions a m o n g

them, and the mechanisms by which they contribute

to disparities in cancer care and prevention. Our efforts

i nclude support to the NCI-sponsored Special

Populations Networks for Cancer Awareness Research

and Training, examination of specific ways in which cancer incidence and mortality are disproportionate for certain poulations (e.g., cervical cancer in rural U.S.),

development of patient education materials for low-literacy populations, collaborations to increase access to and

involvement in clinical trials, and training for new scientists focused on health disparities. In 2003, we will use

funding increases to expand our research efforts in gap

areas, foster better dissemination and use of research

findings, and further increase access to clinical trials by

special population groups. We will support new Centers

for Population Health and Cancer and special grants for

continuing education of health care providers.

Informatics and Information Flow

To assist the cancer research community in keeping

pace with the flood of information stemming from

new scientific discovery, NCI needs to develop and

provide informatics systems that facilitate resource

sharing and the translation of emerging findings into

public health benefits. NCI has built a Cancer

Informatics Infrastructure to supply standardized

bioinformatics support and integration of NCI’s

diverse research initiatives. Within this framework,

we are developing the innovative tools required to

connect people with the information they need. 

In 2003, we will use funding increases to enhance

integration of the data and tools resulting from NCI’s

priority initiatives, establish informatics applications

and services based on a common set of operating

principles and standards and make them available to

cancer researchers, support planning and public communication activities, establish a network of bioinformatics research centers, provide funding supplements

to NCI-supported research organizations for development of informatics systems, and promote informatics

training for biomedical research settings.

Cancer Research Training and Career

Development

Scientists of the future will need to be trained in multiple disciplines, able to work in teams to understand

the multifaceted nature of cancer, and better prepared

to translate discoveries into public benefit. NCI is

employing a variety of individual and institutional

training and career development awards to meet the

needs of new and established investigators and NCI’s

anticipated research priorities. We have focused

increased resources on career development for M.D.s

in cancer research, behavioral and population scientists, minority scientists, and scientists in highly technical fields important to the future of cancer research. 

We also are more effectively integrating education

programs for health practitioners and the public

through improved national networking and use of

communication technologies. NCI will use new

funding in 2003 to more adequately prepare scientists

to work in multidisciplinary environments; reverse

the migration of physicians from research to practice;

increase the number of population, behavioral, and

public health scientists; create a research workforce

that is ethnically and racially diverse; and attract and

integrate technical and informatics experts into 

cancer research. 

EXTRAORDINARY OPPORTUNITIES

FOR INVESTMENT

O

ur focus on six priority areas with extraordinary

potential to impact the pace and direction of 

cancer research have shown significant results and

will be continued into 2003.

Genes and the Environment

As we better understand the interplay between inherited susceptibility to cancer and environmental risk

factors, we will be able to develop more meaningful

approaches to cancer prevention, early detection, and

treatment. NCI has begun building capacity in this

area through consortia of investigators who are 

pooling data and resources to compile the large data

sets required for this kind of study. We also are examining approaches for assessing and measuring 

environmental exposures, advancing research to discover and characterize cancer predisposing genes, and

supporting the development of a number of tools for

use in gene discovery and characterization such as

mouse models of human cancers. We also have 

established an infrastructure to support intervention

trials on inherited susceptibility to cancer. In 2003,

NCI will use new funding to support studies to identify additional environmental risk factors and susceptibility genes and determine their interactions, 

develop new ways to assess and measure environmen6 The Nation’s Investment in Cancer Research
tal exposures, and identify and investigate how other

genes and environmental factors modify the 

expression of cancer predisposing genes. 

Cancer Imaging

With the power of new imaging technology,

researchers and health care providers can generate

much clearer and more detailed pictures of organs

and tissues, and they can use “functional imaging” for

the visualization of physiological, cellular, or molecular processes in living tissue. NCI has supported 

In vivo Cellular and Molecular Imaging Centers to

provide essential infrastructure and career stability to

investigators in this emerging field. We also are fostering the development of new imaging contrast

agents and molecular probes, making equipment and

personnel available to improve technologies and

techniques for imaging small animals, and assessing

the value of computed tomography scanning in

screening patients for colon cancer (“virtual

colonoscopy”). With new funding in 2003, NCI will

be able to advance imaging technology development

and use by expanding the discovery, design, and

development of novel imaging agents and devices,

integrating molecular and functional imaging methods into therapeutic clinical trials, increasing clinical

trials of imaging methods and technologies, and

accelerating the development and clinical testing of

image-guided interventions.

Defining the Signatures of Cancer Cells:

Detection, Diagnosis, and Therapy

With the aid of new technologies, scientists are working to read and understand the unique, identifiable

characteristics of cancer cells known as molecular signatures. Our ability to read these signatures will

allow us to differentiate among tumors at the molecular level and devise treatments targeted at specific

cancers. NCI provides researchers with a variety of

resources for study in this area such as catalogs of

molecular changes in cancer, tissue resources, and

i nformatics tools. The Early Detection Research

Network has begun describing molecular signatures

that may be used for the early detection of breast,

esophageal, and other cancers. New funding in 2003

will be used to expand the development and availability of molecular and analytic resources, make tissue

resources available to researchers, apply molecular

signatures to the study and validation of animal models for human cancer, support new approaches for the

early detection and diagnosis of cancer, and characterize aberrant molecular interactions in cancer.

Molecular Targets of 

Prevention and Treatment

Our increasing knowledge of the molecular changes

that cause a cell to become cancerous is opening a

whole new avenue to drug development. Agents that

target these molecular changes have potential to

selectively delay, stop, or reverse the growth of cancer

cells without harming surrounding healthy tissue and

promise to be less toxic and more effective than current drugs. To respond to this research opportunity,

NCI has rallied the necessary resources for laboratory,

animal, and clinical studies and has begun to identify

numerous potential molecular targets as an early step

in cancer prevention and treatment drug discovery.

NCI will use new funding in 2003 to distinguish and

use cellular targets for the discovery of new anti-cancer

agents; develop assays to identify possible treatments

for cancer; acquire large libraries of natural and synthetic compounds; develop a translational research

program that will closely link molecular imaging,

cancer signatures and molecular targets; and facilitate

the steps necessary to turn a compound into a targeted drug ready for clinical use.

Research on Tobacco and 

Tobacco-Related Cancers

The devastating impact of tobacco use and tobacco

smoke exposure on the incidence of cancer is both

compelling and conclusive. We need to better understand the genetic, biological, behavioral, and social

components of tobacco use, addiction, smoking 

cessation, and how to prevent, detect, and treat

tobacco-related cancers. New evidence is helping to

better explain why some people are more vulnerable

than others to DNA damage caused by tobacco exposure. Research on the early detection of lung cancer

suggests that it may soon be possible to identify cancers in smokers and former smokers at a much earlier

and more treatable stage. Recent studies of teen

smokers have identified psychological factors that

increase the risk of becoming addicted. NCI will use

new funds in 2003 to expand efforts to define the biological, behavioral, and social bases of tobacco use

and addiction; accelerate progress in understanding

the interplay among tobacco, other exposures, and

genetic susceptibility; and develop, test, and disseminate more effective interventions to prevent and

Executive Summary 7
8 The Nation’s Investment in Cancer Research

treat tobacco use and tobacco-related cancers.

Cancer Communications

People now have more ways than ever to get information, and the future holds even more choices.

NCI is working to optimize the use of communications tools to meet the information needs of various

groups while enhancing the absolutely essential interaction of patients with their doctors and nurses.

Digital Divide Pilot Projects have demonstrated the

potential for using computer technology to address

the information needs of underserved populations.

Five new Centers of Excellence in Cancer

Communications Research will be established in

2002 to encourage focused interdisciplinary studies,

increase the number of investigators, and train scientists to conduct cutting-edge research directly. 

In 2003, NCI plans to expand activities to more fully

address the communication needs of underserved

populations, continue the Centers of Excellence, provide support for the dissemination of research results,

and add to the menu of communication choices

available for information about cancer.

PLANNING NATIONAL AGENDAS FOR

DISEASE-SPECIFIC RESEARCH

W

hile we have learned much that is broadly applicable to cancer through our core research programs and Extraordinary Opportunity initiatives,

NCI must be equally alert to the specific tendencies

and behaviors of each unique type of cancer. This is

why NCI plans, promotes, and carries out an ambitious program of disease-specific research, charting

the course for these efforts primarily through advice

from experts participating in Progress Review Groups

(PRGs). NCI carefully addresses PRG recommendations by modifying and supplementing existing

research programs, encouraging scientists to apply for

disease-specific research funding, and developing new

initiatives when needed. PRGs have been completed or are underway for breast, prostate, colorectal,

pancreatic, lung, gynecologic, kidney and bladder

cancers, brain tumors, and leukemia, lymphoma, and

myeloma. PRGs on stomach/esophogeal, liver/bile

duct, and skin cancers are planned. 

The Nation’s Investment in Cancer Research

NCI’s Budget Request for Fiscal Year 2003

(dollars in thousands)

Fiscal Year 2002 President’s Budget $4,177,204

Increase to Core Budget 305,753

NCI’s Challenge Increase

Enhancing Investigator-Initiated Research 121,543

Centers, Networks, and Consortia 81,250

National Clinical Trials Program 433,000

Studying Emerging Trends in Cancer 22,700

Quality of Cancer Care 14,000

Reducing Cancer-Related 

Health Disparities 52,700

Informatics and Information Flow 95,000

Cancer Research Training and

Career Development 58,000

Subtotal Challenge 878,193

Extraordinary Opportunities Increase

Genes and the Environment 55,500

Cancer Imaging 69,800

Defining the Signatures of Cancer Cells 75,000

Molecular Targets of Prevention 

and Treatment 42,500

Research on Tobacco and

Tobacco-Related Cancers 67,000

Cancer Communications 19,050

Subtotal Opportunities 328,850

Total FY 2003 Budget Request $5,690,000
Highlights of Progress 9

O

ne of every two men and one of every three

women in the United States will develop

some type of cancer over the course of their

lives. Approximately 8.4 million Americans alive

today have a history of cancer. The consequences

are enormous: 

■ Nearly 25 percent of all deaths in our country

are due to cancer. Cancer is the second leading

cause of death in the U.S., ranking behind only

heart disease.

■ Medical care expenses for cancer patients and

survivors add up to $60 billion annually, about

five percent of all dollars spent on health care in

the U.S.

■ The toll in pain, suffering, and loss of prod u c t i v ity and income is less easily measured, but keenly

felt by the more than one million patients newly

diagnosed with cancer each year, their families,

and communities. 

There is some encouraging news, however.

Figures reported in the most recent Annual Report to

the Nation on the Status of Cancer

1

show that from

1992 through 1998, cancer incidence rates declined

in men and cancer death rates declined in both

men and women. This promising trend is due to

the earnest efforts and ardent determination of so

many in our country to find better ways to prevent

and more effectively treat cancer in all its forms.

Recent advances reported here provide snapshots of

a few of the thousands of research projects that NCI

sponsors each year that together bring us ever closer to reaching our goal to achieve a future when all

cancers are uncommon and easily treated. 

PREVENTING AND CONTROLLING

CANCER

Cigarette Promotions Influence Smoking

Among Youth2

In a study of nearly 500 elementary and high school

students in Vermont, researchers explored whether

promotional activities for tobacco influence the

smoking behaviors and beliefs of adolescents. Results

of the study suggest that exposure to tobacco marketing does influence youthful attitudes and beliefs

about smoking. Investigators found that the likelih o od that adolescents will start smoking increases

after they acquire cigarette promotional items such as

hats or t-shirts with tobacco company logos. 

These findings underscore the harmful effects on adolescents of tobacco advertising and suggest that eliminating cigarette promotional campaigns could

reduce adolescent smoking. 

Personality Variables Predict Adolescent

Smoking

3

A group of scientists recently determined that better

understanding the personality characteristics of adolescents who become smokers can provide key

insights for designing effective prevention strategies.

These investigators evaluated more than 3,000 fifth

graders for factors such as a propensity toward rebelliousness, risk-taking behavior, problem-solving abilities, and susceptibility to peer compliance and

approval. Following up with the students at the end

of high school, they found that rebelliousness and risk

taking had the strongest predictive value for future

smoking behavior. In light of these findings, the

researchers suggested that smoking prevention

Highlights of Pr o g re s s

1 The Annual Report to the Nation on the Status of Cancer is a collaborative effort of the National Cancer Institute, the Centers for Disease Control and Prevention, 

the National Center for Health Statistics, the American Cancer Society, and the North American Association of Central Cancer Registries.

2 & 3 See pages 83-87 for more information on NCI Tobacco and Tobacco-Related Research initiatives.
10 The Nation’s Investment in Cancer Research

programs should address the needs and expectations

of rebellious and risk-taking youth and should begin

no later than fifth grade. 

Experts Recommend Continuing

Promotion of Fruit and Vegetable s

4

An outside panel of experts recently evaluated NCI’s

decade-long efforts to encourage Americans to

include at least five servings of fruits and vegetables in

their daily diets through the Five A Day Program.

After considering the science underlying the program,

its implementation, and accomplishments, the group

recommended that it continue under NCI’s leadership

while partnering more closely with other NIH institutes, Federal agencies such as the Department of

Agriculture and the Centers of Disease Control and

Prevention, and the produce industry. In addition,

the evaluation report recommends that NCI continue

and expand monitoring of fruit and vegetable consumption in the U.S. as well as its research in related

areas such as cancer communications, behavior

change, and the mechanisms by which fruit and vegetable consumption reduce cancer risk. 

DETECTING CANCER

New Technology May Improve Lung

Cancer Detectio n5

A major obstacle to understanding and treating the

abnormal lesions that are the first sign of lung cancer

is that they are often not visible with bronchoscopy, a

technique by which physicians use a thin, lighted tube

to examine the lungs. Some clinicians have reported,

h o w e v e r, that bronchoscopy using ultraviolet (UV)

light fluorescence may be a more sensitive technique

for detecting these lesions. In an effort to explore this

question, investigators in an NCI-funded Specialized

Program of Research Excellence (SPORE) in Lung

Cancer carried out the first controlled trial comparing

the two techniques. Both approaches tended to pick

up irregularities that were not associated with disease,

but scientists found that UV fluorescence was more

than four times as likely as white light bronchoscopy

to correctly identify precancerous lesions. 

Genetic Testing of Stool Samples Detects

Most Colorectal Cancer s

6

Because colorectal cancer cells are shed into the

stool, testing stool samples can be an easy and noninvasive way to detect colorectal cancer. Exploring

this opportunity, one team of investigators has shown

that the majority of colorectal cancers can be detected by screening stool samples for the presence of three

genes with tumor-associated alterations — T P 5 3, K -

R A S, and B AT 2 6. More studies now are needed to

determine the specificity of these genetic tests for

detecting colorectal cancer in patients without symptoms. 

“Optical Biopsy” Provides a Less Invasive

Method for Detecting Cance r

7

Another investigator is developing an imaging technique that may permit patients of the future with certain types of cancer to undergo “optical biopsies,”

allowing their physicians to diagnose or rule out cancer

without the need for tissue samples. Using a technique

known as optical coherence tomography (OCT), 

scientists have been able to capture ultra-high resolution images of esophageal and gynecologic tissues,

allowing them to identify cancerous lesions in these

sites. Other organs and surfaces that may be imaged

with OCT include the gastrointestinal system, the

b l a d d e r, the lungs, and skin. In the future, health care

providers may be able to improve diagnosis and treatment by attaching catheters and endoscopes to OC T

instrumentation, sparing patients the added time and

pain associated with more invasive procedures. 

Proteomics Offers Hope for New

Prevention, Detection, and Treatment 

NCI has teamed with the Food and Drug

Administration to create a Clinical Proteomics

Program. Proteomics is the systematic study of protein expression and function and an important next

phase in our pursuit of molecular medicine. Proteins

comprise the functional machinery of the cell, linking circuits and pathways that transmit information

within the cell and the entire organism. In cancer,

alterations in genes usually cause defects in the corresponding proteins, disrupting the normal communication network of the cell. Using proteomics, cancer

4 See pages 88-92 for information on other NCI Cancer Communications initiatives.

5 See page 24 for more information on the SPORE program and pages 66-70 for more information on Cancer Imaging initiatives.

6 See page 75 for information on other initiatives to develop genetic testing strategies for the early detection of cancer.

7 See pages 66-70 for more information on Cancer Imaging initiatives.
Highlights of Progress 11

researchers are discovering and characterizing disruptions in the protein communication networks that

drive the growth and spread of cancer, knowledge that

will advance early detection, prevention, and drug

development. For example, a group of NCI scientists

has discovered more than 130 proteins that are

altered during the transition from benign to malignant disease in breast, ovarian, prostate, and/or

esophageal cancers. With additional research, these

proteins may serve as early cancer biomarkers or offer

possible targets for therapeutic drug development. 

Center of Excellence Advances Ovarian

Cancer Biomarker Discovery

The earlier ovarian cancer is treated, the better a

w o m a n ’s chance for recovery. Currently, most ovarian

tumors are diagnosed after they have advanced

beyond cure, spurring researchers to look for reliable,

minimally invasive techniques for earlier detection.

For example, tumor markers that can be measured in

b l o od or used in combination with imaging may

allow health care providers to detect ovarian cancer

s o o n e r. Scientists in an NCI-funded Specialized

Program of Research Excellence have conducted an

extensive search for genes that play a role in ovarian

cancer and identified a number of genes never before

associated with this cancer. These include m e s o t h e l i n,

H E 4, E S E - 1, S L P I a, and G P R 3 9. Scientists now are

studying the molecules associated with these genes to

determine whether they can be useful as early detection markers. If so, and tests can be developed to

detect these markers in blood, this research could

have a significant impact on women’s ability to survive ovarian cancer.

TREATING CANCER

Breast-Conserving Therapy Is At Least

As Cost Effective as Mastectomy

The choice of treatment for breast cancer depends on

many factors, including the size and stage of the

t u m o r, a woman’s age, other medical conditions, and

costs. In a study of nearly 1,700 breast cancer

patients 35 and older with early-stage breast cancer,

researchers compared the cost of care for mastectomy

with that of breast-conserving therapy (BCT). At six

months after diagnosis, the medical care costs associated with BCT were higher than for mastectomy.

The cost difference disappeared over time, however,

and by five years after surgery, the medical care costs

of BCT were less than those for mastectomy, possibly

due to the expenses associated with the higher complication rates of mastectomy or later surgical reconstruction of the breast. This study suggests that breastconserving therapy is at least as cost-effective as mastectomy and should be weighed equally in treatment

considerations about cost. The larger lesson, h o w e ve r, is that short-term and longer-term expenses associated with cancer care may be quite different, and

that both considerations should inform health care

policy decisions.

Phase I Trials Suggest Vaccines for Lung

and Colon Cancers

Although the idea of treating cancer with a vaccine

that stimulates the bod y ’s immune system to kill

tumors is generating exciting results for several cancers, success with lung and colorectal cancers has

been more elusive. Recently, scientists have taken a

new approach that has produced promising results in

a Phase I clinical trial. Researchers first isolated from

tumor tissue a portion of carcinoembryonic antigen, a

protein usually found only in fetal tissue but abundantly expressed in non-small cell lung, colon, and

other cancer cells. They next delivered the isolated

antigen to the immune system using an innovative

m e t h od that seems to heighten the immune response.

Researchers hoped that vaccinated patients would

p r oduce antibodies to attack the novel antigen and

consequently the tumor cells that express it. Five of

the twelve patients in the study did respond to the

vaccine, two with dramatic tumor regression. These

are promising findings for a Phase I trial, and if more

extended clinical trials demonstrate its effectiveness,

this approach could lead to a new therapy for lung,

colorectal, and perhaps other cancers.

Early Hairy Cell Leukemia Trial Results

In Complete Remissions

A new immunotherapy for hairy cell leukemia, a cancer of the immune system, has produced impressive

results in a preliminary clinical trial. The treatment

works by using a specially designed molecule known

as BL22 to deliver a deadly toxin directly to the hairy

cell leukemia cells. Scientists made BL22 by joining

portions of an endotoxin made by the bacteria

Pseudomonas aeru g i n o s a with an antibody that recog-
12 The Nation’s Investment in Cancer Research

nizes and binds to CD22, a protein found on the outside of hairy cell leukemia cells. BL22 is a small molecule designed to get to the tumor quickly and with

less toxicity to the bod y. When BL22 reaches its target, the cancer cell internalizes the deadly toxin by

natural mechanisms and dies. Of the 16 patients with

hairy cell leukemia who participated in this preliminary trial, 11 experienced complete remission and

another two partial remission after BL22 immunothera p y. These early clinical results show promise for BL22

tr e a t m e n t of hairy cell leukemia and other cancers

that express CD22.

Metastatic Melanoma Patients Experience

Regression with Immunotherapy

Melanoma is the most rapidly increasing cancer in

the United States and is virtually lethal once it has

spread beyond the initial site. Recent metastatic

melanoma studies provide some of the first examples

of the successful application of specific immunotherapy for human cancer based on an understanding of

the molecular basis of the immune response against

the disease. For example, many patients vaccinated

with gp100 melanoma antigen,8found on the outside

of melanoma cells, have produced immune cells that

attack their cancer. In a preliminary trial, one-third

of all metastatic melanoma patients experienced

tumor regression when this vaccine was administered

along with the immune stimulating cytokine,9

Interleukin-2 (IL-2). Patients are experiencing substantial tumor regression in pilot studies of vaccination with a number of other antigens characteristic of

melanoma cells, without the help of IL-2 or other

immune boosting cytokines. In recent studies, some

of the cancer attacking immune cells were removed

from patients and allowed to increase in number in a

laboratory culture. Transferring larger quantities of

the immune cells back to the patient resulted in additional cancer regressions. Researchers have begun

exploring molecular and genetic characteristics of

antigens for breast, ovarian, prostate and lung cancers, and similar treatment approaches are being

applied to forms of these cancers. 

UNDERSTANDING CANCER AND 

ITS CAUSES 

Tumor Growth May Be Stopped By

Depriving Cancer Cells of Oxygen

One strategy for stopping tumor growth is to selectively starve cancerous tissue for oxygen. A n g i o g e n e s i s

refers to the bod y ’s ability to grow new blood vessels

to supply tissues low in oxygen, a process necessary for

tumor growth but not for routine bodily functions. If

we learn how to stop this process, we should be able

to arrest tumor growth. Scientists have learned that

the mammalian cell uses the protein hypoxiainducible factor (HIF) to help turn angiogenesis on

and off. When HIF is present, it turns on the genes

that start the angiogenesis process. At normal levels

of oxygen the cell has a mechanism that continuously breaks down HIF. During hypoxia, such as occurs

during tumor growth, another mechanism makes a

small change to the structure of HIF so that it is resistant to degradation. HIF levels increase, blood vessels

g r o w, and the new tumor thrives. Scientists are

searching for possible drugs to target the HIF oxygen

sensing and signaling pathways to stop angiogenesis

without harming healthy cells. 

Reversing the Silence of a Gene May

Make Cancer Therapy Effective

Neuroblastoma is the most common solid childhood

tumor outside the brain area. Despite major advances

in cancer chemotherapy and bone marrow transplantation, the long-term survival rate for children with

aggressive forms of this disease remains very low.

Cancer geneticists are working on a new treatment

idea based on a recent finding about the gene c a p s a s e

8, which may be involved in a set of difficult to treat

neuroblastoma cases. In these neuroblastomas, c a psase 8 does not do its job, because it is either missing

or is chemically altered and rendered silent by a DNA

methylation process. Scientists found that neuroblastoma cells without capsase 8 activity grown in the

laboratory are protected against a number of cancer

therapy drugs directed against DNA targets.

Researchers are now studying the possibility of using

demethylation agents to reverse the chemistry that

silences capsase 8, thus rendering the neuroblastoma

8 An antigen is a protein or protein fragments located on the outside of a cell.

9 A ctyokine is a protein or protein-like substance naturally released by cells that have a biological effect on other cells. IL-2 is produced by certain white blood cells and can help

boost immune response.
Highlights of Progress 13

cells susceptible to the chemotherapeutic agents.

No Connection Found Between Cellular

Telephone Use and Brain Tumors

The use of hand-held cellular phones involves 

placing a small transmitter that emits radio frequency radiation next to the head. Given the unknown

cancer risk posed by this radiation and the important

public health implications, NCI scientists included

cell phone use in a comprehensive study on the causes of brain tumors. Approximately 800 adult brain

tumor patients and 800 controls (adults without brain

tumors) from three medical institutions in the United

States were questioned about their cell phone usage.

Researchers found that regardless of years of use or

number of minutes of use per day reported, there was

no increased risk of brain tumors for cell phone users

compared to non-users. Brain tumors also did not

occur more frequently on the side of the head on

which cell phone users reported holding their phone.

While the NCI study (1994-1998) was conducted at

a time when analogue phones were primarily used,

there is no evidence at this time that cancer risk

differs for the higher frequency digital phones more

commonly used tod a y. 

Scientists Identify Chemosensitive

Gliomas

Gliomas are malignant tumors of the brain that arise

from g l i a l cells, a type of cell that provides support and

insulation for neurons of the brain. Most are quickly

fatal despite treatment, but the prognosis depends

heavily on the specific type of glioma. Patients with

o l i g odendroglioma, for example, respond well to combined treatment with the drugs procarbazine, lomustine, and vincristine with approximately two-thirds

experiencing long-term remissions. Only recently,

h o w e v e r, have scientists begun to identify which

patients would respond to the combined treatment.

They are learning how to predict response based on

the genetic mutations present in the glioma tissue.

For example, patients with altered portions of chromosome 1 and 19 tend to respond much better to

chemotherapy than those with mutations in the genes

P T E N, E G F R, and C D K N 2 A. This research will

improve the ability of physicians to recommend

appropriate treatment for patients. Patients with

responsive tumors will increase their chances of survival when they are treated earlier. Other patients

may be spared ineffective and toxic chemical treatments and offered alternative therapies.

Racial and Ethnic Differences in Prostate

Cancer Need Further Study

The Prostate Cancer Outcomes Study is following

over 3,000 men to learn more about the results of different therapies and their effect on quality of life.

One recent report drawing on data from the study

examined racial and ethnic differences found among

men who developed advanced prostate cancer.

Researchers found that African American men have

the greatest risk of developing advanced disease (12.3

percent). This rate is higher than that of Hispanic

men (10.5 percent) and about twice that of nonHispanic Whites (6.3 percent). Differences in socioeconomic status, symptoms, and tumor characteristics

seem to account for the differences between nonHispanic Whites and Hispanics, but do not explain a

significant portion of the African American disparities. Investigators suggested that further research on

biologic markers, genetic susceptibility factors, and

additional socioeconomic factors such as use of

health care systems, distance from health care, diet,

l i t e r a c y, and health beliefs is needed to sufficiently

describe these disparities. 

Other Research Highlights 

Drugs for Prostate Cancer, page 95

Lung Cancer Detection, page 96

Breast Cancer Treatment, page 97

Centers of Research Excellence, page 28

Clinical Trials, page 30

Cancer Surveillance, page 35 

Quality of Care Patterns, page 40

Health Disparities, page 49

Cancer Imaging, page 70

Cancer Genome Anatomy Project, page 52

Early Detection Research Network, page 75

Molecular Classification of Tumors, page 75

Targeted Drug Development, page 78

Tobacco-Related Cancers, page 84

Cancer Communications, page 88

Mouse Models of Human Cancers, page 58

Story of STI571 Drug Discovery, page 76
14 The Nation’s Investment in Cancer Research

Our Role in

Cancer Research

T

h e NCI works toward this goal in two major

ways. We provide vision and leadership for

c a n c e r research across the United States and

around the world, and we work to ensure that the

results of research are used in public health programs

and clinical practice to reduce the burden of cancer

for all people. Building on past discoveries and technological advances, we plan, conduct, coordinate,

and support cutting-edge research and its application.

We encourage creativity and innovation in all of our

endeavors; support development of, access to, and use

of new technologies by cancer researchers; and back

up these approaches by providing research training

and career development opportunities and maintaining support mechanisms and collaborative environments to link scientists with their colleagues and with

critical technological and information resources. 

As leader of the National Cancer Program, NCI

provides the public with scientifically sound cancer

information using all forms of communication carefully designed to meet the needs and preferences of

cancer patients, persons at risk, their families, and

those who care for them. The ultimate purpose of

these activities is to help move research findings into

clinical practice, chart and improve the quality of

cancer prevention and care, and reduce disparities in

the burden of cancer.

HOW WE PLAN AND SET PRIORITIES

T

he NCI engages in a number of ongoing planning

and priority setting activities to ensure that we are

responsive to new discoveries and opportunities and

make the best use of our resources. Our leaders work

closely with NCI staff, the researchers we support,

and representatives from the scientific, medical, and

advocacy communities to determine what is needed

and how best to move the science forward. 

We plan research that will comprehensively

address critical unanswered questions covering the

many forms of cancer and the various populations

that experience them. We work to integrate basic,

behavioral, population, and applied research through

translational activities and strive to identify new

opportunities as well as gaps and barriers to progress

that help us create new programs and improve

existing ones.

Program assessment is key to keeping our research

portfolio balanced and our support structure strong.

To implement recommendations arising from assessments, we convene scientists from diverse settings to

assist NCI staff with redesigning programs and developing new initiatives. We track implementation and

regularly report on our progress. 

Our planning activities encompass three key

components required for a strong cancer research

enterprise: 

■ M a i n t a i n i n g a sound research infrastructure

and building capacity for the future. We give

priority to developing the technological and

personnel resources needed to support changing

scientific and resource needs and the translation

of new knowledge and emerging technologies

into clinical practice.

1

■ Capitalizing on extraordinary scientific 

o p p o r t u n i t i e s . We seek opportunities that

promise to provide profound insights into cancer – those opportunities that hold greatest

potential to lead to major improvements in our

ability to prevent, control, detect, diagnose, and

treat cancer.

2

The National Cancer Institute’s goal is to stimulate and support scientific disco very and

its application to achie ve a future when all cancers are uncommon and easily treated.

1 See page 20 for information on “NCI’s Challenge” and our current infrastructure development priorities.

2 See page 60 for information on NCI’s “Extraordinary Opportunities for Investment,” the current scientific priority areas we are pursuing.
Our Role in Cancer Research 15

■ Disease-specific research . We continually

assess our portfolios and plan for the research

needed to uncover the biological and other

characteristics that are unique to specific types

of cancer.

3

HOW WE WORK

We sponsor and conduct cancer research.

The National Cancer Institute’s primary mission is to

sponsor and conduct cancer research, and we use our

budget to support a broad range of research that will

expand our understanding of cancer and develop

improvements in prevention and care. Some investigators conduct basic laboratory research on genes

that may cause cancer. Others are studying the incidence of cancer in specific populations, such as farm

families and former smokers. Still other scientists

focus on translational research, such as developing

tests to identify patients who carry genes that may

make them susceptible to cancer, or clinical trials to

determine the effectiveness of new diagnostic tools or

drugs for treating cancer. 

The largest portion of research funds goes to support the work of scientists conducting research in universities, teaching hospitals, and other organizations

outside the NIH. Proposals submitted by these 

extramural investigators are selected for funding by

peer review, a process by which cancer experts from

around the country identify outstanding science and

the most needed areas of discovery by evaluating the

approximately 5,000 new research proposals NCI

receives every year. With guidance and oversight

from program experts in NCI’s Divisions of Cancer

B i o l o g y, Cancer Treatment and Diagnosis, Cancer

Prevention, and Cancer Control and Population

Sciences, cancer research is conducted with NCI

funding in nearly every state in the U.S. and more

than 20 foreign countries. 

Another portion of our research dollars stay at the

NIH in Maryland, where some 400 NCI principal

investigators are at work. These intramural investig a t o r s in NCI’s Center for Cancer Research and

Division of Cancer Epidemiology and Genetics focus

on the rapid translation of basic laboratory research

to clinical testing and long-term epidemiologic and

genetics studies. Recent changes in the structure of

the intramural program promise to further enhance

their role in the Nation’s cancer research effort. 

As the number of NCI’s research initiatives has

grown in recent years, so too have the responsibilities

of our scientific managers and administrators. 

Research management and support budgets are used

for the critical technical and administrative services

required for NCI to carry out its work. They include

central administration functions, overall program

direction, grant and contract review and administraN ew NCI I n t ra m u r al Structure Maximizes

C o l l a b o ra t i o n

T he Center for Cancer Research (CCR) was re c e nt l y

e s t a b l i s hed within NCI’s Int ra mu ral Researc h

P ro g ram to bring toge t her pre v iously separa t e

b a s ic and clinical scie nce activities and allow

t ra ns l a t io nal re s e a rch the best opportunity to

flourish. By cre a t i ng a highly int e ra c t i v e, int e rd i sc i p l i nary enviro n me nt that maximizes the use of

re s e a rc her expertise and techno l o g y, re s e a rc he r s

a re better able to perform cutting edge basic,

t ra ns l a t io nal, and clinical investig a t io ns and 

facilitate commu n ic a t ion, int e ra c t ion, and quic k

re s p o nse to pro m i s i ng re s e a rch find i ng s. 

The CCR facilitates tra ns l a t io nal re s e a rch by 

p ro v id i ng a de f i ned process for and support to

re s e a rc hers study i ng pro m i s i ng targeted tre a tme nt s. “Faculties” bring toge t her sc ie ntists who

work in differe nt disciplines but on similar canc e r

re s e a rch pro b l e ms across the Ins t i t u t e, both 

i nt ra mu ral and ex t ra mu ral. The fa c u l t ie s p ro v ide a

v e nue for sharing info r ma t ion, info r mal peer

re v ie w, and successful collabora t io n .

To further enc o u ra ge int e ra c t ion of scie nt i s t s,

both ex t e r nal and NCI re s e a rc hers can become

a d j u nct appointees within CCR labora t o r ie s. The s e

a p p o i nt me nts allow re s e a rc hers to work mo re closely

with other labora t o r ies than would have been 

possible in tra d i t io nal collabora t io ns. Ad j u nc t

i n v e s t igators attend me e t i ngs and become

involved in the da y - t o - day work of the labora t o r y.

I nt e rd i s c i p l i nary tra i n i ng pro g ra ms are also

u nder de v e l o p me nt through the CCR to enc o u ra ge

y o u ng investigators to ex p l o re pro m i s i ng new are a s

of scie nc e, such as those fo u nd at the int e r s e c t io n

of chemistry and bio l o g y, statistics and bio l o g y, or

p a t hology and ge ne t ic s. 

3 See page 93 for more information on how Progress Review Groups (PRGs) assess the scientific needs and opportunities that are critical to advancing research on specific forms of cancer.
16 The Nation’s Investment in Cancer Research

tion, personnel, program coordination, and financial management.

In addition to direct research funding, NCI offers

cancer scientists a variety of useful research tools and

s e r v i c e s . Among the research resources made available to investigators at little or no cost are tissue 

samples, mouse models of cancers, statistics on cancer

incidence and mortality, databases of genetic information, and software for analyzing statistical and

genetic data.4

NCI devotes approximately four percent of its

annual budget to preparing the next generation of

cancer researchers and ensuring a steady flow of well

trained investigators. Each year, we provide c a n c e r

research training and career development o p p o r t u n i t i e s

to more than 2,000 graduate students, postdoctoral 

fellows, and oncologists. Some of this research training takes place on the NIH campus, but most goes on

in universities and teaching hospitals around the U.S. 

We foster research through collaborations

and partnerships.

To ensure that we use public funds to greatest advantage, NCI encourages collaborative research and

partners with other organizations in numerous ways.

We began one of our longest-running partnerships by

establishing the Cancer Centers Program in the

early 1960s. Congress encouraged the expansion of

the Program to improve the quality of cancer care by

bringing cancer scientists and oncologists together in

the same setting with patients and their families.

Tod a y, two-thirds of the 60 centers funded by NCI are

Comprehensive Cancer Centers , so designated

because of the breadth and depth of the research conducted by their investigators and their role in public

education and outreach. 

N C I ’s Centers of Research Excellence a l s o b r i n g

together groups of cancer scientists from different

areas of expertise. Centers of Excellence are smaller

in scale than other NCI Cancer Centers and generally focus on one or a few types of cancer or scientific

areas. For example, NCI’s Specialized Programs of

Research Excellence (SPOREs) focus on translational

research for specific cancers. Other examples of NCI

Centers of Research Excellence are the

Transdisciplinary Tobacco Use Research Centers,

In Vi v o Cellular and Molecular Imaging Centers, and

the soon-to-be established Centers of Excellence in

Cancer Communications Research. All of these centers support interactive, interdisciplinary research,

make research resources and flexible exploratory

funds available to investigators, and provide research

training and career development opportunities. 

The largest collaborative research activity sponsored by NCI is our clinical trials program for testing

cancer treatments, diagnostic tests, and interventions

for preventing cancer. With the participation of

more than 10,000 medical school and private practice physicians in NCI’s Clinical Trials Cooperative

Group Program and Community Clinical Oncology

Program, NCI supports over 1,300 clinical trials a

year involving more than 200,000 patients.5 N C I

also brings investigators together through n e t w o r k s

like the Early Detection Research Network, which

assembles groups of scientists to identify markers and

develop tests to detect early signs of cancer, and 

consortia like the Mouse Models of Human Cancer

Consortium, in which scientists from around the

world share their expertise and resources in creating

strains of mice that develop cancers similar to those

seen in humans.

NCI also fosters collaborative work through partnerships with other Federal and state agencies w i t h

roles in improving the Nation’s health. For example,

much of the data on cancer trends available today has

been collected and analyzed through the combined

efforts of NCI, the Centers for Disease Control and

Prevention (CDC), and state cancer registries. 

In addition, NCI has joined forces with five other

Federal agencies to work on a number of projects

aimed at improving the quality of cancer care, such as

efforts to raise the rates of colon cancer screening

among veterans and the elderly. 

S c i entists, medical experts, and advocates also work

t o g e t h e r to help shape NCI’s policies and programs

through a number of standing and ad hoc a d v i s o r y

g r o u p s . The National Cancer Advisory Board provides overall guidance for NCI and a final assessment

of the research proposals selected for funding

through peer review. The Board of Scientific

Counselors evaluates the progress, performance, and

p r oductivity of the Institute’s intramural research

programs and scientists through regular site visits to

NCI. The Board of Scientific Advisors plays a

similar role for NCI’s extramural program, reviewing

the progress of ongoing programs and providing feed4 For a directory, go to resresources.nci.nih.gov.

5 See page 29 for more information about the NCI National Clinical Trials Program.
Our Role in Cancer Research 17

back on proposed new research activities. On a regular basis, NCI convenes Progress Review Groups of

scientific and medical experts and advocates to

examine the research needs and opportunities for

specific types of cancer. NCI also is strongly influenced by the President’s Cancer Panel’s assessment

of progress and problems in the Nation’s effort to

reduce the burden of cancer. 

In addition to their membership on other NCI

advisory groups, advocates provide the NCI Director

broad advice on program and research priorities

through the Director’s Consumer Liaison Group, an

all-consumer advisory committee. NCI also solicits

the advice of patients and their family members

through the recently created Consumer Advocates in

Research and Related Activities (CARRA) program.

This pool of 150 advocates will participate in Progress

Review Groups assessing research needs for specific

cancers, provide advice on the design of clinical trials, and review education materials we develop. 

We work to ensure that people benefit

from our research. 

The results of NCI-sponsored research consistently

provide cancer patients and those who care for them

with information, tools, and tests that impact cancer

prevention and care and help people make better

health choices. For example, once its effectiveness

was confirmed in clinical trials, oncologists were

quick to adopt the use of tamoxifen in the care of

breast cancer patients. Likewise, since studies established the link between diet and cancer risk, more

and more of us now strive to include five servings of

fruits and vegetables in our daily diets. 

Many of these advances reach the medical community and the public through medical journals and

news reports, but NCI helps move the process along

through a range of cancer communications a c t i v i t i e s .

We provide information on scientific advances to the

media and the public using an extensive array of

information resources including a toll-free telephone

service available in all regions of the country, printed

brochures and educational packages, and We b - b a s e d

information on cancer and clinical trials. NCI-sponsored researchers work to create the best methods for

reaching all who need to learn about cancer, recent

research findings, and opportunities to participate in

clinical trials. 

When NCI-sponsored research results in discoveries that may lead to new drugs, devices, or diagnostic

tests, federal laws encourage universities – and NCI –

to pursue c o m m e r c i a l i z a t i o n by licensing them to

i n d u s t r y. In addition, NCI intramural investigators

can also collaborate with industry through arrangements known as Cooperative Research and

Development Agreements (CRADAs). It is through

such an agreement between NCI and a major pharmaceutical company that investigators are continuing

to follow chronic myelogenous leukemia patients

treated with the recently approved anti-cancer agent

GleevecTM, to determine its long-term effects. 

Another way NCI makes a difference in peoples’

lives is through our efforts in reducing the differences

in the occurrence of cancer, its treatment and outcomes among various racial and ethnic groups. 

Our programs include research into the causes of

health disparities as well as measures to translate

research results into better health for groups at high

risk for cancer. For example, NCI-sponsored investigators are using insurance data to examine the extent

to which African American, Hispanic, and White

patients are receiving recommended treatments for

colon cancer. In addition, NCI is supporting field tests

of smoking cessation and weight control programs targeted to the needs of specific racial and ethnic groups. 

H ow We Spend Our Budget

Nearly 90 perc e nt of our budget is directly de d ic a ted to cancer re s e a rch, unde r s t a nd i ng how and why

c a ncer strikes and de v e l o p i ng impro v e me nts in its

p re v e nt ion and care. The re ma i nder of our budge t

is used for re s e a rch tra i n i ng and career de v e l o pme nt, the commu n ic a t ion of cancer info r ma t io n ,

a nd re s e a rch ma na ge me nt and support.

E x t ra mu ral Research 73%

I nt ra mu ral Research 16%

R e s e a rch Tra i n i ng and

C a reer Developme nt 4%

C o m mu n ic a t io ns 3%

R e s e a rch Ma na ge me nt

a nd Support 4%
Each year, as mandated by the National Cancer Act of 1971 (P.L. 92-218), the

National Cancer Institute (NCI) prepares a budget request for supporting the cancer

research workforce with the technologies and resources it needs, building on research

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

This annual proposal is provided directly to the President of the United States in the

fall of each year for formulating the President’s budget request to Congress.

This document also serves as NCI’s strategic plan and is intended for use by NCI staff; the

researcher community; professional organizations; advisory groups; cancer information,

education, and advocacy organizations; and public and private policymakers whose

decisions affect cancer research and care in America. It is our hope that the 

information will inform and inspire all who read it to join the fight against cancer.

The National Cancer Institute’s Budget Request

for Fiscal Year 2003

. . . to achieve a future when all cancers are uncommon and easily treated.
The Nation’s Investment in Cancer Research

Research Project Grants 46.8%

Other Grants 1.1%

Research Management and Support 3.3%

Research Support Contracts 10.4% Cancer Control Operations 2.8%

Training and Education Grants 3.1%

Distribution of 2003 Budget Request ($5,690,000,000)

Distribution of 2003 Requested Increases 

($1,512,796,000)

Funding for extramural research, primarily

through investigator-initiated Research

Project Grants (RPGs), comprises the

largest part of the NCI core budget.

Increases through the NCI Challenge and

Extraordinary Opportunity initiatives contribute to the expansion of research 

supported through RPGs. NCI funds

about 4,500 RPGs each year to nearly 600

institutions across the United States at an

average cost of approximately $400,000

per grant. If fully supported, our budget

request for Fiscal Year 2003 would add

$638 million to the funds available to 

support investigator-initiated research.

RE S E A R C H PR O J E C T GR A N T S

NCI intramural research focuses on projects conducted by some 400 scientists

located on the NIH campus. These

researchers build on their proximity to

the NIH Clinical Center and the synergism among NIH Institutes to support the

rapid translation of basic laboratory

research to the clinic and to maintain a

special focus on long-term epidemiologic

and genetics studies. 

IN T R A M U R A L RE S E A R C H

Sixty NCI-supported Cancer Centers

serve as hubs for cutting-edge research,

high quality cancer care, and outreach

and education for healthcare providers

and patients. Centers of excellence like

the 27 SPOREs use flexible funding to

pursue questions related to specific forms

of cancer and to move disease-specific

research quickly from the laboratory to

the patient. Funding increases will allow

NCI to expand the number of Cancer

Centers and SPOREs and broaden their

range of activities. 

CA N C E R CE N T E R S A N D SP E C I A L PR O G R A M S

O F RE S E A R C H EXC E L L E N C E ( S P O R E S)

Research Project Grants 43.9%

Intramural Research 4.4%

Cancer Centers 6.2%

SPOREs 2.4%

Clinical Trials

Infrastructure

28.0%

Training and Education

Grants 1.7%

Cancer Control Operations 1.0%

Clinical Trials Infrastructure 12.6%

SPOREs 2.5%

Cancer Centers 5.3%

Intramural Research 12.1%

Other Grants 0.3%

Research Management and Support 2.5%

Research Support Contracts 9.6%
Research Project Grants (RPGs)

Ongoing $1,271,453 $1,460,698 $1,645,963 $1,645,963 $1,645,963

New (New and Renewal) 498,805 454,939 471,317 685,860 908,160

Subtotal 1,770,258 1,915,637 2,117,280 2,331,823 2,554,123

Small Business Innovation Research 74,593 85,120 110,120 110,120 110,120

Total RPGs 1,844,851 2,000,757 2,227,400 2,441,943 2,664,243

Intramural Research 593,581 619,443 641,743 683,243 686,243

Cancer Centers 205,507 206,202 213,625 286,375 299,375

Specialized Programs of

Research Excellence (SPOREs) 91,475 107,452 111,320 140,320 143,320

Clinical Trials Infrastructure

Cooperative Clinical Research 154,278 173,386 179,628 515,128 528,128

Community Clinical Oncology Program 26,208 119,482 123,784 188,784 188,784

Subtotal 180,486 292,868 303,412 703,912 716,912

Training and Education Grants

National Research Service Awards 60,495 68,310 70,769 73,769 73,769

Research Career Program 54,970 57,828 59,910 74,610 74,610

Cancer Education Program 20,521 21,671 22,451 22,451 24,951

Minority Biomedical Research Support 3,479 4,638 5,138 5,138 5,138

Subtotal 139,465 152,447 158,268 175,968 178,468

Cancer Control Operations 141,110 144,461 149,662 152,662 159,862

Research Support Contracts 372,743 444,550 460,554 542,754 589,604

Research Management and Support 142,518 152,084 157,559 174,559 190,559

Other Grants 42,720 56,940 59,414 59,414 61,414

Total NCI 3,754,456 4,177,204 4,482,957 5,361,150 5,690,000

Cancer Control included above ** 457,965 511,058 538,431 648,881 783,431

18 The Nation’s Investment in Cancer Research

NCI Budget Request for Fiscal Year 2003

N CI supports clinical trials carried out by

approximately 10,000 investigators at some

1,700 U.S. hospitals and cancer centers

each year. Over 1,300 trials will be 

conducted in 2001 involving some 200,000

patients. Many of these trials make possible

the testing of targeted agents like STI571

that hold promise for more effective, less

invasive, cancer prevention and treatment.

About three-quarters of this funding is for

treatment trials and the other quarter supports prevention trials. The largest portion

of additional funding will be used to

increase physician reimbursement for 

participation in trials.

CL I N I C A L TR I A L S IN F R A S T R U C T U R E

NCI funds approximately 170 institutions

and 2,000 individuals each year through

extramural cancer research training programs to prepare the next generation of

scientists and clinicians to use new technologies and work effectively in interdiscip l i n a r y, collaborative research environments. Increased funding will be used to

enhance these programs and to support the

participation and growth of scientists 

within underserved populations.

TR A I N I N G A N D ED U C AT I O N GR A N T S

N C I ’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 tobacco and tobacco-related

research, research to reduce cancer- r e l a t e d

health disparities and improve the quality

of cancer care, information dissemination,

and a host of other similar activities. 

CA N C E R CO N T R O L * *

2001 

Operating

Budget 

2002 

President’ s

Budget Core

Core &

Challenge

Core, C h a l l e nge,

& Extra o rd i na r y

O p p o r t u n i t ie s

2 0 0 3 B u d g e t R e q u e s t

(dollars in thousands)
Research Project Grants (RPGs) 

Ongoing $185,265 $185,265

New (New and Renewal) 16,378 $214,543 $222,300 453,221

Subtotal 201,643 214,543 222,300 638,486

Small Business Innovation Research 25,000 25,000

Total RPGs 226,643 214,543 222,300 663,486

Intramural Research 22,300 41,500 3,000 66,800

Cancer Centers 7,423 72,750 13,000 93,173

Specialized Programs of

Research Excellence (SPOREs) 3,868 29,000 3,000 35,868

Clinical Trials Infrastructure

Cooperative Clinical Research 6,242 335,500 13,000 354,742

Community Clinical 

Oncology Program (CCOPs) 4,301 65,000 69,301

Subtotal 10,543 400,500 13,000 424,043

Training and Education Grants

National Research Service Awards 2,459 3,000 5,459

Research Career Program 2,082 14,700 16,782

Cancer Education Program 780 2,500 3,280

Minority Biomedical Research Support 500 500

Subtotal 5,821 17,700 2,500 26,021

Cancer Control Operations 5,201 3,000 7,200 15,401

Research Support Contracts 16,004 82,200 46,850 145,054

Research Management and Support 5,475 17,000 16,000 38,475

Other Grants 2,474 0 2,000 4,474

Total Requested Increases 305,753 878,193 328,850 1,512,796

*Increases over the 2002 President’s Budget. 

NCI Budget Request 19

Core

NCI’s

Challenge

E x t ra o rd i na r y

O p p o r t u n i t ie s To t a l

Requested Increases for Fiscal Year 2003*

Research support contracts play a role in

program efforts across the Institute. Areas

that utilize contracts are diverse and

include such areas as drug development,

cancer control research, information 

dissemination, and support to epidemiological research.

RE S E A R C H SU P P O R T CO N T R AC T S

Research management and support budgets are used for the critical technical and

administrative services required for NCI to

carry out its work. They include central

administrative functions, overall program

direction, grant and contract review and

administration, personnel, program coordination, and financial management.

RE S E A R C H MA N AG E M E N T A N D SU P P O R T

Other grants go to support partnerships

and shared resources, scientific evaluation,

and workshop and conference support.

OT H E R GR A N T S

(dollars in thousands)
NCI’s Challenge FY 2003 Increase

(dollars in thousands)

Enhancing Investigator-Initiated Research $121,543

Centers, Networks, and Consortia 81,250

National Clinical Trials Program 433,000

Studying Emerging Trends in Cancer 22,700

Quality of Cancer Care 14,000

Reducing Cancer-Related Health Disparities 52,700

Informatics, and Information Flow 95,000

Research Training and Career Development 58,000

Total Challenge $878,193

N C I ’s 

C h a l l e n g e

W

e are entering the 21st century with everexpanding knowledge and an array of sophisticated tools for continuing the fight against

c a n c e r. The challenge before NCI is to build and

continually enhance a research system that will allow

the scientific community to apply new discoveries

and emerging technologies. We need mechanisms

that will promote and reward innovative thinking,

aid cross-fertilization of ideas among disparate scientific disciplines, and enhance collaborations among

government, academia, and industry. We must develop and maintain a cadre of trained scientists from a

variety of disciplines. And we must address special

societal concerns and other barriers that jeopardize

our Nation’s ability to provide the best possible treatment to cancer patients, ensure equal access to information and care, and offer current and future scientists sufficient opportunities to obtain research funding and other kinds of support. 

NCI must provide the vision, creative environments, and diverse resources needed to ensure an easy

flow between the increasing number of discoveries

and advances in cancer research and the scientific

c o m m u n i t y ’s ability translate these findings into clinical application. If the pace of discovery can be

likened to speeding down a superhighway, our current

ability to apply these findings still progresses at the

slower pace of a country road. Where the two intersect, a bottleneck prevents a tremendous number of

g o od ideas from moving forward. Our challenge is to

continue to expand and smooth the country road,

hastening discoveries to their application in interventions across the continuum of cancer care – from

prevention and early detection to diagnosis, treatment, life after cancer, and the end of life. 

To respond to this challenge, we identified six key

areas for investment in our 2001 and 2002 proposals

and will continue addressing these in 2003.

Beginning with our 2002 proposal, we added new

priority areas to address two persistent barriers to

meeting our challenge: (1) inadequate quality of

cancer care and (2) disparities in access to information, patient care, and research opportunities and

careers. The plans proposed for these challenge

areas describe new research awards or new and

expanded programs and collaborations intended to

help improve the prospects for patients and survivors

of all types of cancers.

20 The Nation’s Investment in Cancer Research

National Clinical Trials

Program 49.3%

Research Training

and Career

Development 6.6%

Informatics and

Information Flow

10.8%

Reducing CancerRelated Health

Disparities 6.0%

Quality of Cancer

Care 1.6%

Studying

Emerging Trends

in Cancer 2.6%

Centers,

Networks,

and Consortia

9.3%

Enhancing

Investigator-Initiated

Research 13.8%
THE CHALLENGE

I

n v e s t i g a t o r-initiated research — research independently conceived and developed by scientists —

has always been the primary means by which biomedical research is conducted. Driven by the 

synergism present at the medical

schools, hospitals, universities, research

centers, and corporations they represent, these investigators ask the critical

questions, explore the options, develop

and test innovative technology, and

make the discoveries that lead to better

cancer care and prevention. 

Recent advances, such as the

sequence of the human genome, new

technologies for identifying molecular

targets within cancer cells, and method s

for discovering and analyzing promising drugs aimed at

each cancer-causing pathway, have provided scientists

with a wider arsenal of approaches and technologies

for research than ever before. However, to take

advantage of these advances, researchers often require

additional resources, in the form of new research tools

and equipment, collaborators from different disciplines, or special support for translational research.

Providing these resources is NCI’s challenge in the

area of investigator-initiated research.

NCI has seen an enormous increase in the need

for funding to allow scientists to fully exploit new

t e c h n o l o g i es and approaches to conducting research.

In Fiscal Year 2001, for example, the cost of research

projects supported by NCI was nearly 15 percent higher than the year before. In response to this trend, we

inevitably are forced to make some compromises in

order to balance the growing number of research

opportunities with the rising costs of research. These

compromises result in NCI awarding fewer research

grants than are endorsed by peer review and supporting

each at a lower level than recommended. Though

reviewer assessments of research applications consistently identify the top 35 to 40 percent as particularly

worthy of support, the proportion actually funded (the

success rate) has averaged only 28 percent in recent

years. Moreover, NCI has been able to maintain this

success rate only by reducing individual grant budgets

an average of 15 percent. A lack of funds — rather

than a lack of exceptional ideas — remains a significant bottleneck in our fight against cancer.

Low success rates and less than optimal funding may prevent some of the

brightest minds of the next generation

from choosing to enter cancer research.

But a sufficient infusion of resources and

funding into investigator- i n i t i a t e d

research will help to ensure that students

considering a career in science, as well as

current researchers, will perceive cancer

research as an appealing and rewarding

profession. 

PROGRESS T OWARD MEETING THE

CHALLENGE

T

he NCI has sought to support and foster investigator-initiated research through a variety of policy decisions and flexible funding options. 

Identifying and Supporting High Priority

Research

NCI takes extra steps to identify and support high 

priority research by:

■ Seeking out and supporting compelling research

proposals that may have been overlooked in peer

r e v i e w, particularly those suggesting dramatically

new or unconventional approaches to understanding cancer. 

■ Giving special consideration to proposals from

clinical researchers and those who respond to NCI

announcements of priority research areas, such as

recommendations from Progress Review Groups

for research related to specific cancers. 

N C I ’s Challenge: Building Our Capacity for the Future

Enhancing Investigator-Initiated Resear c h

G O A L

Accelerate disco veries

and their application b y

expanding and facilitat -

ing researcher access to

resources and ne w

technologies .

NCI’s Challenge 21
22 The Nation’s Investment in Cancer Research

THE PLAN — ENHANCING INVESTIG ATOR-INITIATED RESEARCH 

Objectives and Milestones for Fiscal Year 2003

1. Accelerate the pace of discovery through increased funding for and larger numbers of

competing research grants.

■ Support research projects at the full levels recommended by peer reviewers.

■ Fund, at a minimum, the top 35 percent of competing applications with (1) the highest scientific merit, (2) a less certain probability of success but potential to yield greater reward if they

do succeed, (3) unconventional approaches but unique promise, (4) a focus on areas of extraordinary need in specific fields of investigation or model systems, and/or (5) the involvement of

new investigators.

2. Encourage investigators to commit to careers in cancer research and to propose more

innovative and higher reward projects.

■ Continue to allocate the first 80 to 90 percent of available funds for research project grants

through conventional selection processes while ensuring that proposals from new investigators

are also funded at a rate comparable to those of more established investigators. 

■ Through a special evaluation process, fund particularly innovative and potentially high

reward projects.

3. Facilitate rapid movement from discovery to application by using established 

mechanisms and creating novel special awards to encourage transdisciplinary and 

collaborative research. 

■ Expand supplemental funding to grants to promote new interdisciplinary collaborations that

bring together basic and clinical scientists, such as those fostered by NCI’s Activities to

Promote Research Collaborations Program.

■ Expand researcher access to central resources such as databases, tissue banks, and animal

m odels using funding supplements; centers, networks, and consortia; and cooperative

resource programs. 

Maximizing the Ability to Start Ne w

Projects and Collaborations

NCI seeks to maximize the pace of discovery by providing a broad range of flexible funding options

and promoting collaborations and resource sharing wherever possible by: 

■ Providing opportunities for collaborative study

through awards such as program project grants

(P01s) and cooperative agreements, in addition to

the traditional research project grants (R01s) that

make up the bulk of NCI’s research portfolio. 

■ Expanding the use of award mechanisms that

provide seed funds for promising research. 

In Fiscal Year 2000, the number of small (R03)

and exploratory/developmental (R21, R33)

grants awarded increased more than 25 percent

over the previous year.

■ Making “administrative supplement” funds available to investigators to allow them to take advant a ge of unanticipated opportunities or to pursue

interdisciplinary collaborations. For example,

through NCI’s Activities to Promote Research

Collaborations Program, grantees can apply for

funding to support collaborations to initiate novel

research that pursues unforeseen opportunities,

share resources, develop new technologies, or

organize cross-disciplinary meetings or workshops. 
NCI’s Challenge 23

■ Expand researcher access to technologies that promote interdisciplinary research and collaborations and to the expertise needed to move discoveries to application. 

■ Encourage the development of information technology tools to foster and enhance interdisciplinary communication and collaboration.

■ Double the funding for collaborative research awards such as program project grants and

cooperative agreements for networks in cancer genetics, imaging, early detection, and other

areas.

■ Expand the use of exploratory grants to encourage more patient- and population-based

research.

■ Allow peer review to be the primary determinant of appropriate funding levels for individual awards.

4. Use regular and special award mechanisms to encourage investigation in priority 

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

extraordinary opportunity working groups. 

■ Monitor investigator-initiated research to assess whether these projects alone are meeting

programmatic objectives, such as those identified in specific disease areas.

■ Set aside 10 to 15 percent of funds for Requests for Applications in specifically targeted

areas of need. 

■ Support Program Announcements and investigator-initiated projects that target identified

gaps and/or emerging opportunities. 

■ Enhance coordination within and among initiatives, and increase direct contact with applicants and grantees by increasing levels of extramural staff commensurate with the growth of

the portfolio.

Total $121.5 M

■ Promoting collaborative studies and sharing of

resources through various networks and consortia.

(See page 25.)

Reviewing Research Proposals Better 

and Faster

We review grant applications more effectively and

make awards more rapidly than in the past. This is

possible in large part because of changes such as: 

■ The establishment of a clinical oncology study section in April 2000 by NIH’s Center for Scientific

Review to ensure that applications for clinical

research funding are reviewed by those familiar

with the special issues related to such research.

■ Electronic approval of grant applications by

National Cancer Advisory Board members

between their regularly scheduled meetings, permitting Institute staff to notify recipients earlier

and, in many cases, allowing research projects to

begin sooner than anticipated. This new procedure reduces the standard nine-month funding

cycle by more than a month for most applications.
24 The Nation’s Investment in Cancer Research

To d a y ’s Research Investments Shape the Number of Resear c h e rs To m o r r ow

W hen, as in re c e nt years, the perc e nt a ge of re s e a rch proposals that NCI funds (the success rate) 

a v e ra ges less than 30 perc e nt, and gra nts ro u t i nely are less than fully funde d, young people may be disc o u ra ged from pursuing careers in cancer re s e a rch and opt for prof e s s io ns in mo re stable or well-paying

f ie l d s. Faced with such odd s, ma ny clinic ia ns in particular may choose a career in private pra c t ice over

c l i n ical re s e a rch. Basic cancer biology scie ntists may choose ano t her career altoge t he r. 

T hu s, it is not just funds for tra i n i ng per se that influence the number of future re s e a rc he r s. 

(See page 20.) The success rate of the Research Project Gra nt (RPG) pool also ma kes its mark. First,

ma ny tra i nees de p e nd on RPGs awarded to their me nt o r s, ra t her than fo r mal tra i n i ng award s, 

for fina nc ial support of their tra i n i ng. If their me ntors’ gra nts are not funde d, tra i nees often have no

i m me d iate me a ns to cont i nu e. Second, upon completion of their tra i n i ng, new investigators today ge ne rally cannot expect much fina nc ial support from the university or me d ical school whe re they work, but

i nstead must de p e nd on RPG awards for their salaries as well as for re s e a rch support. Without suc h

g ra nt s, these investigators are unable to pursue their chosen career in an acade m ic setting. Clearly, the n ,

re duc t io ns in the numbers of awards and the perc e nt of re c o m me nded dollars actually awarded have 

p rofo u nd effects on the next ge ne ra t ion of cancer re s e a rc he r s. 

To cont i nue to address the ma ny questio ns re ma i n i ng in cancer re s e a rch, NCI must assure a steady supply

of future re s e a rc hers in the tra i n i ng pipeline. This re q u i res mo re than support for the tra i n i ng itself. 

It also re q u i res ma i nt e na nce of the lig ht at the end of the tunnel, in the form of re a s o nable odds fo r

o b t a i n i ng gra nts to sustain the careers of future cancer re s e a rc he r s.

NCI Research at Your Fingertips 

“What research is NCI supporting in pancreatic cancer?” “How much of this research is devoted to

biology or etiology versus treatment and prevention?” “How much of NCI’s total research effort is in

early detection, diagnosis and prognosis?” These are all easy questions, but until recently very difficult to answer.

In the spring of 2001, NCI launched a new Web site, the Cancer Research Portfolio, the most comprehensive, easy to use source of information about current NCI-supported research. Investigator-initiated grants, contracts, clinical trials, and NCI’s intramural research are for the first time accessible in

one place, one database, and, now, available to the public on a Web site. Viewers can search, browse,

and sort NCI research in ways never possible before. For example:

■ Cancer patients and advocates can see exactly what NCI is funding by cancer site and disease as well

as across broad scientific areas.

■ Scientists can more easily identify investigators doing similar work, as well as contacts for multidisciplinary research and collaborations.

■ Congressional staff can view cancer research supported in their states as well as assess the status of

research support across disease site and scientific area.

■ Science policy advisors and NCI staff can use this tool to facilitate cancer research planning and

resource allocation. 

Visit researchportfolio.cancer .gov to learn more about this NCI tool.
THE CHALLENGE

O

ur efforts to translate scientific knowledge into

more effective cancer interventions increasingly

are challenged by the conventional ways in which

research is conducted. With tod a y ’s rapid pace of scientific and technological discovery, NCI must help

researchers create integrated research environments

that foster the multidisciplinary collaborations needed

to address the “big picture” problems in cancer research.

We must functionally link basic, clinical, population,

and behavioral scientists to each other and to newly

developing, diverse fields of science and technology.

Investigators must have easy access to many different

patients and at-risk populations, tissue

banks, new technologies, and state-ofthe-art informatics. They must be able to

work together with ease and flexibility in

multi-institutional research settings as

well as within the same institution.

NCI must continue to create and nurture an overarching structure for research

composed of NCI-designated Cancer

Centers, Centers of Research Excellence,

and research networks and co n s o r t i a .

These centers, networks, and consortia are enhancing

the traditional research enterprise in ways that promote

and facilitate complex scientific interactions, provide

the critical resources essential for the research, and

encourage the easy exchange of information and ideas

through new communication linkages. While these

interactive structures are critical to progress, this challenge also requires that NCI find ways to integrate these

centers and networks with each other when broader

interactions will allow investigators to seek answers to

major questions more efficiently and effectively.

NCI-designated Cancer Centers organize and integrate multidisciplinary research across departments and

schools within a single institution. They provide scientists access to the most advanced technologies and new

research opportunities and bring the benefits of their

research directly to the public in the form of patient

care. They link state-of-the art research and clinical

care activities within the institution and form key partnerships with industrial, community, and state health

organizations outside the institution. (See

c a n c e r.gov/cancercenters for more information.)

For example, the disease-specific Specialized

Programs of Research Excellence, designed to move

discoveries between the laboratory and patient and

population research settings, had their origins in

Cancer Centers. The new Special Populations

Networks for Cancer Awareness Research and

Training are designed to link local, community, and

regional problems of cancer in underserved populations to the broad-based research capabilities of NCIdesignated Cancer Centers. Centers are critical in a

new NCI initiative to incorporate

Minority-Serving Institutions (MSIs) into

N C I ’s cancer research, education, training, and outreach activities. The Cancer

Genetics Network sites are headquartered in Centers. Nearly all the participants in the Mouse Models of Human

Cancer Consortium are in NCI-designated Cancer Centers. Centers have

worked closely with industry in developing new cancer therapeutic agents and

are rapidly becoming significant partners with industry for new technology development. Approximately

70 percent of cancer clinical trials are conducted in

Cancer Centers. 

NCI is planning to establish Regional

Enhancement Cancer Centers to facilitate partnerships between smaller institutions and the large, existing NCI-designated Comprehensive Cancer Centers.

These partnerships will provide patients and populations with much improved access to the newest trials

in early detection, prevention, and therapeutic

research. NCI anticipates that the centers also will

play a key role in integrating and coordinating NCIsupported centers of excellence and networks into one

overarching, unified research framework. 

Centers of Research Excellence bring together

interdisciplinary and translational research teams

focused on a specific disease, mod a l i t y, biologic

N C I ’s Challenge: Building Our Capacity for the Future

C e n t e rs, Netw o r ks, and Consortia

G O A L

Create and sustain

research infrastructures

for collaboration, 

technology support and

development, and access

to resources .

NCI’s Challenge 25
26 The Nation’s Investment in Cancer Research

THE PLAN — CENTERS, NETWORKS, AND CONSORTIA

While NCI’s goal for collaborative research applies to all NCI-designated Cancer Centers, networks, and consortia, this plan focuses primarily on the objectives and resources for the Centers

and SPOREs. Many other research networks are budgeted and discussed in the Extraordinary

Opportunities and NCI Challenge sections throughout this document. 

Goal

Create and sustain research infrastructures for collaboration, technology support and 

development, and access to resources that enable multiple scientific disciplines to address

large problems in cancer that could not be solved by individual investigators.

Objectives and Milestones for Fiscal Year 2003

1. Increase the number and broaden the geographic distribution of NCI-designated

Cancer Centers and create partnerships between Minority-Serving Institutions and

NCI Cancer Centers.

■ Designate one new Cancer Center to bring the total number of centers to 61. $1.25 M

■ Award two new Cancer Center Planning Grants. $0.50 M

■ Establish formal affiliations between Cancer Centers and Minority- Serving Institutions

(MSIs) in the form of 2 comprehensive partnerships and 1 planning grant for a comprehensive partnership to enhance the research capabilities of MSIs, and improve the effectiveness

of Cancer Centers in serving minority communities. (See page 57, Objective 3 for the

training component of these partnerships.) $5.50 M

2. Expand the capacity of Cancer Centers to engage in newly developing areas of research

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

■ Increase funding to all Cancer Centers to encourage scientists in Centers to develop new

technologies and methodologies for entirely new approaches to answering important cancer

research questions. $6.00 M

$7.3 M

$28.5 M

process, or scientific area. They are awarded sizeable

amounts of flexible funding to enable them to rapidly address emerging scientific opportunities. 

The first of these centers, the Specialized Programs

of Research Excellence (SPOREs), were created in

1992 and focus on specific cancers. They serve as highly effective hubs for translational research, moving discoveries back and forth among laboratory, clinic, and

population research settings. To date, SPOREs have

been established in breast, lung, gastrointestinal, ovarian, prostate, genitourinary, and skin cancer. 

(Go to spores.nci.nih.gov for further information.)

The SPORE blueprint has been used to establish

similar programs in other cancer research areas,

including NCI-sponsored Transdisciplinary To b a c c o

Use Research Centers, In Vi v o Cellular and Molecular

Imaging Centers, Interdisciplinary Research Te a m s

for Molecular Target Assessment, and the soon-to-be

established Centers of Excellence in Cancer

Communications Research. Like the SPOREs, all of

these centers support interactive m u l t i d i s c i p l i n a r y

research and provide research resources and flexible

exploratory funds, as well as research training and career

development opportunities. 

Networks and consortia link the expertise and

innovation of scientists from different disciplines and
NCI’s Challenge 27

■ Establish 10 Informatics Planning Activities in Cancer Centers to build, in partnership with NCI,

critical informatics capabilities in data acquisition, analysis, integration, and coordination. $7.50 M

■ Provide additional funding to build the clinical research and population research infrastructure of Cancer Centers. Fund databases that conform to NCI’s clinical informatics infrastructure; support the development and expansion of population databases; provide more core staff

to conduct innovative translational therapeutic and prevention trials; and strengthen the

auditing and data safety and monitoring of human subjects research. $15.00 M

3. Expand and enhance the research of Specialized Programs of Research Excellence

(SPOREs).

■ Expand the SPORE program by adding one in genitourinary cancer, one in lung cancer, two

in leukemia, one in myeloma, one in ovarian cancer, one in prostate cancer and one in skin

c a n c e r. $24.00 M

■ Support development of an Internet platform and research database to enable SPOREs to

exchange research results and to foster communications for sharing resources and developing

collaborative inter- S P ORE research projects. $1.00 M

■ Provide supplements to SPOREs for planning and developing inter- S P ORE research 

projects. $4.00 M

4. Implement a Strategic Supplement Program for taking advantage of high priority scien -

tific opportunities that can be completed in a short time frame (1 to 2 years):

■ In response to opportunities identified by NCI program managers of Cancer Centers, Centers

of Excellence, Networks, and Consortia $5.00 M

■ In response to scientific advice from outside advisory groups (e.g., Progress Review Groups)

$10.00 M

Management and Support

To t a l

$29.0 M

$15.0 M

$1.5 M

$81.3 M

diverse research backgrounds to address important

questions and issues about cancer. For example, the

Cancer Genetics Network addresses the issue of inherited predisposition to cancer and is linking its goals and

objectives to those of SPOREs and NCI-designated

Cancer Centers. The Mouse Mod e l s of Human

Cancer Consortium will work closely with SPOREs to

develop mouse models that reflect various precancerous

and cancerous stages of human cancer. The American

College of Radiology Imaging Network, the newest of

N C I ’s cooperative groups, is evaluating and developi n g

a new generation of imaging concepts and tools with

device manufacturers and other technology developers.

The Early Detection Research Network, which facilitates the discovery, development, and initial steps in

clinical validation of molecular markers and assays

that detect early signs of cancer, is already interacting

with SPOREs and other interdisciplinary teams of scientists. The Special Populations Networks are involvi n g underrepresented communities in establishing

research priorities and conducting research that will

benefit these populations. Investigators in several

brain tumor consortia are exploring new biologic

approaches to pediatric and adult brain tumors, testing

promising new treatments, and evaluating innovative

ways of administering existing therapies.
28 The Nation’s Investment in Cancer Research

PROGRESS T OWARD MEETING THE

CHALLENGE

T

hrough its Cancer Centers Program, NCI has

established the foundation for an overarching

research framework that will bring diverse scientific

disciplines together across institutional boundaries.

NCI-designated Cancer Centers continue to

evolve as key strategic partners of NCI. In 2001,

NCI added a Center in Missouri and will fund a new

planning grant for developing a Center in South

Carolina. In addition, the number of Cancer

Centers with the “Comprehensive” designation

increased in 2001 to 38. NCI has also been working

with institutions in more than 10 other states to

develop Cancer Centers. 

NCI launched the Minority Institution/Cancer

Center Partnership (MICCP) Program in Fiscal Ye a r

2001 by funding 2 comprehensive partnerships, 2 planning grants for comprehensive partnerships, and 12

planning grants dedicated to more focused collaborative projects and programs ranging from research to

training. This program reaches out to the 5 major

minority institutions with medical schools, as well as

to more than 300 smaller institutions dedicated to

educating African Americans, Hispanics, Native

Americans, and other groups underrepresented in biomedical research. Research-intensive NCI Cancer

Centers, together with culturally sensitive MSIs, offer

an entirely new set of opportunities for training more

minority scientists, expanding the cancer research

capability of MSIs, and focusing more research and

community outreach programs of Cancer Centers on

understanding and addressing minority health disparities. In the next year, the MICCP will seek ways to

integrate its efforts with NCI’s Special Populations

Networks for Cancer Awareness Research and

Training and the Minority Biomedical Support Grant

Program, sponsored by the National Institute of

General Medical Sciences at the NIH.

As NCI’s Specialized Programs of Research

Excellence (SPOREs) have become more established, SPORE investigators have begun to make 

significant contributions to translational research 

(see Spotlight on Research, page 24). Similarly, the

multidisciplinary collaborations fostered by other

centers of research excellence are starting to yield

some impressive results. Research advances from

Transdisciplinary Tobacco Use Research Centers are

described on page 86; those from In Vi v o Cellular and

Molecular Imaging Centers can be found on page 67. 

S i nce their start in 1992, NCI’s Specialized Pro g ra ms of

R e s e a rch Exc e l l e nce (SPOREs) have grown to inc l ude 27

c e nters focused on tra ns l a t io nal re s e a rch for breast, lung ,

g a s t ro i nt e s t i nal, ovarian, pro s t a t e, ge n i t o u r i na r y, and skin

c a nc e r. Recent advances testify to their value:

■ T he discovery that smo kers who carry certain ge ne

types are less likely than others to successfully quit.

This find i ng raises the possibility that specially tail o red cessation pro g ra ms may help these smo ke r s.

■ A better approach to de t e c t i ng the early sig ns of lung

c a nc e r. Investigators fo u nd that the use of fluo re s c e nt

l ig ht in bro nc hoscopy dra ma t ically improved phy s ic ia ns’ ability to ide ntify the early sig ns of lung canc e r.

■ C o n f i r ma t ion that family clusters of panc re a t ic canc e r

have a ge ne t ic basis. After tra c k i ng relatives of panc re a t ic cancer patie nts since 1994, re s e a rc hers re c e ntly confirmed that those with two or mo re re l a t i v e s

with panc re a t ic cancer are at hig her risk for the dise a s e. This find i ng pro v ides important info r ma t ion fo r

t hese relatives and their phy s ic ia ns and supplies scie ntists with a vital first step toward ide nt i f y i ng the

re s p o nsible ge ne s.

■ P ro m i s i ng results in an initial clinical trial of a tre a tme nt vaccine that stimulates the immu ne system of

p a nc re a t ic cancer patie nts to take action against the i r

t u mo r s. Investigators have now ex p a nded testing of

this new tre a t me nt to a larger number of patie nt s.

■ C o n f i r ma t ion that varia t io ns in the molecular prof i l e s

of differe nt types of breast tumors can yield important

clues about the prospects for relapse and long - t e r m

p a t ie nt survival. 

In the coming years, the pro g ram will cont i nue to establish centers on the cancers curre ntly under study while

ex p a nd i ng to inc l ude centers devoted to every major cancer site. The expected sche dule for ex p a ns ion can be

fo u nd at s p o re s. n c i . n i h . g o v.

S P O T L I G H T O N R E S E A R C H

Results Show Value of SPOREs
NCI’s Challenge 29

THE CHALLENGE

C

linical trials, a crucial component of NCI’s

research program, are the final, definitive step in

testing new approaches to cancer prevention, diagnosis, and treatment. Our National Clinical Tr i a l s

Program essentially is a laboratory without walls,

through which NCI has a tangible and direct impact

on the survival and quality of life of patients with

c a n c e r. 

N C I ’s clinical trials system is complex, involves

many participants, and requires collaboration at all

levels – between investigators and physicians, industry and academia, academia and NCI,

and NCI and industry. Adding to this

c o m p l e x i t y, cancer clinical trials have

undergone a number of dramatic

changes in recent years. Progress in

cancer biology, genetics, immunology,

molecular biology, and imaging technology has accelerated, creating new

opportunities to improve clinical practice. As cancer researchers around the

country have identified the molecular

changes that cause a normal cell to become cancerous, the number of new anti-cancer agents that target

these changes has rapidly grown, triggering an entirely new approach to the development of cancer drugs

and a rapid growth in NCI-sponsored clinical trials

for treating and preventing cancer. 

At the same time, advances in informatics and

electronic communications have led to new

approaches to communication and data reporting and

analysis in the clinical research setting, providing new

opportunities to enhance the efficiency of clinical trials

and speed their results to the care of cancer patients.

N C I ’s cooperative groups — networks of investigators who conduct clinical trials — have begun to

incorporate many of these advances into their clinical trials, but much work remains to be done. 

Despite progress made to date, many barriers to

clinical trials participation persist. In particular, the

reimbursement that NCI provides physicians for their

role in clinical trials often falls far short of their costs

and is well below what the pharmaceutical industry

provides. Physicians who take part in clinical trials

often must hire additional nursing and data management staff to ensure that patients fully understand the

risks and benefits of participation, track participating

patients, and collect and report the necessary data. A

1999 survey of oncologists by the American Society

of Clinical Oncology found that although many

physicians preferred NCI-sponsored cooperative

group clinical trials, inadequate reimbursement for

the costs and time required for data reporting were

barriers to participation. 

While NCI has improved the availability of clinical trials information to

patients and health care professionals

(see page 89) and has doubled its reimbursement over the past several years, it

still lags far behind actual costs and

industry standards. This problem is

compounded in cancer prevention trials

because many thousands of patients

often are needed to evaluate preventive

measures and these patients must be followed for longer periods of time. 

N C I ’s challenge is to ensure that we overcome the

barriers to participation in clinical trials and that we

capitalize on the latest developments in cancer

research, informatics, and management to address our

most important questions in cancer prevention and

treatment. 

PROGRESS T OWARD MEETING 

THE CHALLENGE

I

n our ongoing efforts to improve the speed and efficiency with which cancer clinical trials are cond u c t e d , NCI recently centralized the common administrative, financial, and data collection activities of its

clinical trials cooperative groups. Through an online

Cancer Trials Support Unit site unveiled in 2000,

cooperative group investigators can now download

N C I ’s Challenge: Building Our Capacity for the Future

National Clinical Trials Pr o g ram in Treatment and Prev e n t i o n

G O A L

Ensure that clinical trials

address the most 

important questions in

treatment and pr evention

and are broadly 

accessible .
30 The Nation’s Investment in Cancer Research

clinical trial protocols and other information, enr o l l

patients in clinical trials, arrange for reimbursement of

research costs, and receive alerts when new trials

begin. In 2002, oncologists outside the cooperative

groups also will be permitted to enroll their patients in

these clinical trials. 

S i m i l a r l y, the four cooperative groups conducting

studies on cancer in children merged into a single new

C h i l d r e n ’s Oncology Group. This consolidation is

expected to potentially double the number of doctors

and hospitals involved in any given study and allow

trials to be completed more quickly. With cure rates

for new childhood cancers now reaching 70 percent,

the new cooperative group will be able to devote more

of its energies to the less common childhood cancers,

for which cures have not been as forthcoming.

Over the past two years, clinical trials have cont i n u e d to contribute to improvements in survival

and quality of life for patients with a wide variety of

cancers. For example, recently completed clinical trials have determined that:

■ Cervical cancer, still the second leading cause of

cancer death in women around the world, can be

treated more effectively by combining cisplatin

chemotherapy with radiation treatment. It is estimated that this treatment can save 2,000 

additional lives each year in the United States

and considerably more – perhaps hundreds of

thousands – worldwide. 

■ The combination of chemotherapy and radiation

following surgery substantially prolongs the 

survival of patients with stomach cancer. 

■ For patients with metastatic kidney cancer, 

surgery to remove the kidney can add months to

patients’ lives. 

■ Preoperative chemotherapy prolongs the survival

of patients undergoing bladder cancer surgery. 

■ In the most aggressive cases of prostate cancer, 

radiation therapy combined with the optimal application of hormone treatments leads to longer 

s u r v i v a l .

■ The use of cyclooxygenase-2 (COX-2) inhibitors

reduces the number of colon polyps in patients

with the genetic disorder Familial Adenomatous

Polyposis. Without treatment, patients with this

condition typically develop numerous polyps,

increasing their risk for colon cancer. 

The recent improvements in cancer therapy

described above generally combine advances in conventional anti-cancer treatments with surgery,

c h e m o t h e r a p y, or radiation. But the past decade also

has seen an explosion in our understanding of tumor

biology and immunology, which has led to the i d e n t ification of a vast array of new molecular targets a t

which to direct treatment and prevention interventions. The cellular pathways and interactions involved

in these molecular targets are extraordinarily complex

and inter-related, and they require scientists to develop new techniques and tests to identify patients

whose tumors contain the relevant targets. 

As a result, clinical trials of targeted agents often

involve laboratory studies to better define the presence of targets and drug effects in the tumors of individual patients undergoing treatment. Indeed, more

than half the cancer treatment trials initiated by

N C I ’s cooperative groups over the last two years have

included correlative studies. This trend is also

increasingly seen in cancer prevention trials involving chemopreventive agents. 

Along with the discovery of more and more therapeutic targets for cancer, there has been a huge

increase in the number of new anti-cancer agents in

drug development. According to the Pharmaceutical

Research and Manufacturers of America, more than

400 anti-cancer agents were in development in 2001,

up from fewer than 100 in the late 1980s. Similarly,

the number of pharmaceutical and biotechnology

companies developing anti-cancer agents nearly

quadrupled over the same period, rising from 45 to 170.

Despite this large increase in corporate involvement, NCI’s role and the public-private partnerships

it brokers continue to be essential. NCI collaborates

with industry in the development of many promising

investigational agents for treatment and prevention

by sponsoring clinical trials for them. Because pharmaceutical companies tend to seek FDA approval or 

licensing of a new agent only for a single tumor type,

N C I ’s involvement in the drug development process

helps ensure that new agents are evaluated against

the full range of cancers for which they may be effective and in combination with treatments such as surgery and radiation therapy. These collaborations

bring new treatments and prevention strategies to

patients years earlier than would otherwise occur.

Figure 1 illustrates the rapid expansion of clinical tri-
NCI’s Challenge 31
32 The Nation’s Investment in Cancer Research

THE PLAN — N ATIONAL CLINICAL TRIALS PROGRAM IN TREA T M E N T

AND PREVENTION

Goal

Ensure that NCI’s clinical trials program is poised to address the most important medical

and scientific questions in cancer prevention and treatment quickly and effectively through

state-of-the-art clinical trials that are broadly accessible to cancer patients, populations at

risk for cancer, and the physicians who care for them.

Objectives and Milestones for Fiscal Year 2003

1 . Identify and address compelling clinical questions confronting physicians and their patients

struggling with cancer or at high risk of cancer.

■ Expand clinical trials planning so that critical treatment and prevention questions are

addressed across the major types of conditions experienced by patients. $1.00 M

■ Expand State of the Science meetings to identify important research questions and define a scientific research agenda to address them. $1.00 M

■ Provide additional research funds for scientific leadership support for researchers who chair

studies in addition to caring for patients and for statisticians; together they are responsible for

writing, monitoring, and analyzing NCI-sponsored, high-priority Phase III trials. $3.00 M

■ Increase translational research funds for clinical correlative studies to uncover the mechanisms

of action, response, and resistance underlying new treatments and preventive strategies and to

translate basic biology from the laboratory to clinical practice. $8.00 M

■ Support a national tissue resource system to facilitate rapid evaluation of new assays and relevant clinical correlations as new targets are identified. (See page 72, Objective 2.)

■ Fund tissue and specimen banks to store material from cancer patients undergoing treatment

and from those at risk of developing cancer to allow later studies of drug effectiveness, molecular abnormalities, and clues to tumor initiation and progression. $4.00 M

■ Develop and make widely available molecular assays required to characterize/classify tumors.

(See page 80, Objective 2.)

2 . Enhance the ability and flexibility of the clinical trials system to respond quickly and

effectively to scientific opportunities emerging from the vast expansion of molecular

targets discovery, new drug discovery, and translational research.

■ Create flexible collaborations among investigators to facilitate multi-institutional clinical trials,

projects, and consortia.

■ Integrate scientific strategic planning to include cross-disciplinary input (e.g., oncology and

diagnostic imaging) and project teams.

■ Incorporate other relevant research questions into treatment and prevention trials, and utilize

the clinical trials infrastructure more broadly. 

■ Incorporate behavioral, epidemiologic, outcomes, and other relevant research to effectively

address cancer questions in specific tumor types and patient populations. 

■ Incorporate the evaluation of relevant biomarkers into clinical trials.

$17.0 M

$5.5 M
NCI’s Challenge 33

3 . Increase the pace of development and clinical testing of promising new therapeutic and

preventive agents. 

■ Over 2 to 3 years, substantially increase the number of promising agents entering NCI-sponsored clinical trials, triple annual patient accrual to early clinical trials of promising agents, and

substantially increase the number of pivotal or proof-of-principle early clinical trials.

■ Expand resources for the Rapid Access to Intervention Development (RAID) and Rapid Access to

Preventive Intervention Development (RAPID) programs. (See page 81, Objective 4.)

■ Increase funding for early treatment and prevention agent development and for Interdisciplinary

Research Teams for Molecular Target Assessment to develop the necessary assays, tools, and

approaches to assess the effects of promising new agents on their molecular targets. $20.00 M

■ Support a rapid grant review process for mechanism-based clinical trials. 

■ Support the NCI intramural clinical trials program by increasing the numbers of data managers, research nurses, biostatisticians, and clinicians available to support a critical mass of clinical investigators; continue to develop the net-Trials database system (see page 52); and continue

the Tissue Array Research Program to identify key molecular alterations in cancers. $15.00 M

4 . Double the rate at which Phase III trials are completed. 

■ Shorten the duration of patient accrual to national trials (approximately 5 years at present) by 50 percent, thereby substantially increasing the number of new treatments or interventions that can be

e v a l u a t e d .

■ Provide funds to adequately support data management and enable substantially greater physician and

patient participation in clinical trials. $350.00 M

■ Increase physician reimbursement to $3,500 per patient for treatment and prevention trials to 

adequately cover the additional nursing and data management costs required to participate in 

clinical trials. 

■ Double the number of patients accrued to treatment and prevention trials over 1 to 2 years. 

■ Provide follow-up funding to allow physicians to follow patients, report outcome data, and 

address important long-term treatment and epidemiology issues. 

■ Expand the Clinical Trials Support Unit to consolidate the administrative tasks associated with

clinical trials and to provide a single interface for investigators enrolling patients. $20.00 M

■ Provide extensive information about prevention and treatment clinical trials to enable patients

and physicians to make informed choices. (See page 90, Objective 2.)

■ Facilitate clinical trials participation by developing uniform electronic case report forms and

data reporting systems (See page 52, Objective 1.)

5 . Reduce outcome disparities in special populations by increasing access to state-of-the-art

clinical trials in cancer prevention and treatment. (See page 47, Objective 5.) 

Management and Support

Total

$35.0 M

$370.0 M

$5.5 M

$433.0 M
34 The Nation’s Investment in Cancer Research

als in many different tumors, made possible by the

collaboration between Novartis Pharmaceuticals and

NCI-supported researchers to develop GleevecTM. 

As scientists discover more and more about the

basic mechanisms of cancer, they also add to our

knowledge about its prevention, allowing experts to

explore the possibility of averting cancer through

c h e m o p r e v e n t i o n . Unlike conventional approaches

to preventing cancer, which often focus on avoiding

exposure to cancer-causing agents (such as tobacco

and excessive sunlight), chemoprevention actively

intervenes against cancer with drugs or other agents

that stop the transformation of normal cells into cancer cells. 

One of the most widely used chemopreventive

agents today is tamoxifen, a drug that interferes with

the activity of estrogen and was initially introduced as

a treatment for breast cancer. After physicians began

to report that women who had received tamoxifen

following breast cancer surgery were less likely to

develop cancer in their other breast, NCI initiated

the first large breast cancer prevention trial in the

United States to determine whether the use of

tamoxifen could prevent breast cancer in high-risk

women. Initial results from that trial, announced in

1998, indicated that tamoxifen did indeed reduce the

risk for breast cancer, and that its use could be especially beneficial for young women at significant risk

for the disease. But because tamoxifen also carries

potentially serious risks, such as blood clots and

stroke, NCI continues to sponsor other clinical trials

in breast cancer prevention. A major NCI-supported

study is comparing tamoxifen with raloxifene, an

osteoporosis prevention drug that also appears to

lower the risk for breast cancer. 

A number of other NCI-sponsored studies are

e x a m i n i ng the potential for the arthritis drug celecoxib (CelebrexT M) to prevent colon and other cancers.

For arthritis sufferers, celecoxib reduces inflammation

and alleviates symptoms by inhibiting the bod y ’s production of COX-2 enzymes. Researchers suspect that

celecoxib might play a valuable role in cancer prevention because precancerous tissues, such as colon polyps,

also produce COX-2 enzymes, and because epidemiologic studies have shown that arthritis sufferers w h o

regularly use anti-inflammatory drugs have lower rates

of colon cancer. In NCI-sponsored studies thus far,

celecoxib has been found to reduce the number of

colon polyps in patients with Familial Adenomatous

Polyposis, an inherited syndrome that predisposes

them to colon cancer. Other NCI-funded clinical trials are investigating whether celecoxib can prevent

esophageal, bladder, and skin cancers.

What Are Clinical Trials?

C l i n ical trials are re s e a rch stud ies involving

p a t ie nt s, de s ig ned to de t e r m i ne whe t her new dr u g s

or tre a t me nts are safe and effective. Clinical tria l s

a re also ro u t i nely conducted to answer questio ns

about new or ex i s t i ng ways to pre v e nt, dia g no s e,

a nd detect diseases such as cancer and may 

exa m i ne q u e s t io ns such as the psycho l o g ic a l

impact of cancer or ways to improve a patie nt ’ s

q uality of l i f e. In add i t ion, as we learn mo re about

t he me c h a n i s ms of canc e r, the number of canc e r

c he mo p re v e nt ion trials has been steadily inc re a s i ng .

New tre a t me nts or che mo p re v e ntive age nts are

tested on patie nts only after laboratory and 

a n i mal tests have shown pro m i s i ng re s u l t s. 

O nce patie nts are involved, clinical trials ge ne ra l l y

p roceed through four phases. As each phase of

t e s t i ng is completed, the data collected are 

a nalyzed to de t e r m i ne whe t her the age nt is 

s ho w i ng enough of a benefit to cont i nue testing .

T he testing and approval process can take ma ny

years; ho w e v e r, the approval process can somet i mes be accelera t e d, particularly if the age nt is

b e ne f ic ial for patie nts with a form of cancer that

has few tre a t me nt or pre v e nt ion optio ns. 

Phase I – These small tria l s, ge ne rally involving

20-80 patie nt s, focus on de t e r m i n i ng the safety of

a new age nt, ide nt i f y i ng side effects, and 

e s t a b l i s h i ng a safe do s a ge ra nge.

Phase II – With a larger group of patie nts (100-

300), Phase II trials are int e nded to evaluate the

e f f e c t i v e ness of a new tre a t me nt, as well as to

c o nt i nue to test its safety. 

Phase III – These large tria l s, often involving

1,000-3,000 people, pro v ide mo re definitive info rma t ion about a new the rapy’s effectivene s s, 

monitor the occurre nce of side effects, and 

c o m p a re the new the rapy to standa rd tre a t me nt s.

It is only after a Phase III trial has been 

s uccessfully completed that the Food and Drug

Adm i n i s t ra t ion cons iders whe t her to approve a ne w

drug or tre a t me nt for ge ne ral use. 

Phase IV – After FDA approval has been gra nt e d,

Phase IV trials cont i nue to collect info r ma t io n

about tre a t me nt outcomes in various populatio ns

of patie nts and any side effects associated with

l o ng-term use. 

For mo re info r ma t ion about cancer clinical trials or

details about how to participate in a cancer 

clinical trial, go to cancertrials.nci.nih.go v.
NCI’s Challenge 35

THE CHALLENGE

O

ver the past few decades, NCI has worked with

other agencies to create a national cancer surveillance system for tracking cancer trends: the monitoring of cancer incidence, cancer mortality, cancers

that are declining and those on the rise. At this time,

our challenge is to develop a surveillance system that

not only tracks cancer statistics but also helps us form

hypotheses for cancer research, make critical scientific and public health decisions, develop and monitor

prevention and control measures, and assess whether

or not interventions are making a difference. Advances in information

t e c h n o l o g y, increasing diversity in the

U.S. population, and changes in health

care delivery present new challenges to

this task. 

To continue our pivotal role in effective and comprehensive national surveillance, we must improve surveill a n c e in ways that help communities

identify research needs and develop

effective cancer planning and health

p o l i c y. N C I ’s Surveillance, Epidemiology, and End

Results (SEER) program must cover a broader spectrum of the population and compare information on

why people get cancer, how it is treated, and with

what outcomes. We must improve the measures we

use to track cancer risk, screening practices, treatment, quality of life, quality of care, and morbidity.

Surveillance must also integrate information on

health care providers, health systems, cancer communities, and policy into local and regional databases.

We must develop research tools that track cancer

trends more completely and precisely . We must

change the way we make surveillance data available

electronically to ensure privacy and confidentiality.

We need new m odeling techniques to help us explain

trends across the full range of concerns about cancer.

We need geographic information systems to study data

on individuals in relation to potential environmental

exposures. We must refine maps to allow easier application of statistical analyses for measuring patterns and

identifying clusters. And, we must strengthen dissemination of surveillance data to scientists, the public, and

policy makers in a timely manner and in a readily usable

f o r m a t .

PROGRESS T OWARD MEETING THE

CHALLENGE 

T

he NCI has worked with many partners to build a

broader surveillance program that is easily used

for cancer research, planning, and

health policy decisions. We have

expanded SEER (see Spotlight on

Research, p. 38) and made other important improvements. 

We have augmented our data collection on risk, health behaviors such as

smoking and diet, and screening. For

example, we have collected nationwide

tobacco tracking data and conducted an

in-depth evaluation, through the Ca n c e r

Research Network , of tobacco control

activities conducted within medical practices across

the United States. We have enhanced dietary data

collected by the National Center for Health Statistics.

These modifications help us track progress made

towards achieving the Healthy People 2010 nutrition

objectives relevant to cancer control. We released a survey of cancer risk, health behaviors, and screening conducted in collaboration with the National Center for

Health Statistics in the fall of 2001. This provides data

for tracking progress in cancer control health practices,

genetic testing issues, and other cancer-related health

objectives. We also have linked mammographic

screening data in diverse communities to cancer outcomes to provide national measures of mammography

performance. 

NCI has added to its research on the adoption of

new advances in cancer risk assessment, screening,

and treatment and how their use impacts the lives of

p a t i e n t s . For example, a completed national survey on

N C I ’s Challenge: Building Our Capacity for the Future

Studying Emerging Trends in Cancer

G O A L

Expand cancer 

surveillance to impr ove

monitoring of progress in

cancer control and

explain potential causes

of cancer across all 

populations .
36 The Nation’s Investment in Cancer Research

THE PLAN — STUDYING EMERGING TRENDS IN CANCER

Goal

Expand cancer surveillance data systems, methods, communications, and training to improve

capacity for monitoring progress in cancer control and to explain potential causes of cancer

nationally and among diverse populations.

Objectives and Milestones for Fiscal Year 2003

1. Improve cancer registry data by expanding Surveillance, Epidemiology, and End Results

(SEER) coverage, improving the quality of all population-based cancer registries, and

enhancing SEER as a research resource.

■ Refine and harmonize 4 new expansion registries added to SEER to meet data quality 

standards and use the data for reporting and for cancer control activities. $2.00 M 

■ Implement and improve SEER quality assurance procedures and use of data quality 

profiles. $0.50 M

■ Increase coordination of Federal cancer registry programs through innovative information 

technology systems for SEER programs. $0.75 M

■ Support innovative statistical survey research methodology and models for combining data

from diverse sources of the evolving national cancer surveillance data. $0.75 M

2. Expand systems and methods to enhance the quality of cancer control data on risk, health

and behaviors, and screening practices linked to high quality data on cancer outcomes.

■ Continue the Current Population Survey (CPS) Tobacco Use Supplements. (See page 84,

Objective 1.)

■ Improve data quality and measurement of key cancer issues in national and regional data systems. Initiate data tracking systems for cancer control and treatment drugs and for over- t h e -

counter prescription drugs and complementary and alternative therapies. $1.50 M

■ Support development of a restricted access research data center required for linked databases

containing potentially identifiable information. $1.00 M 

■ Continue supporting surveillance screening initiatives. $3.00 M

■ In collaboration with the Agency for Healthcare Research and Quality, develop a 

surveilance and behavioral colorectal cancer screening initiative to raise levels of 

compliance with screening and monitor performance in primary care practices.

■ Explore data systems to monitor the use and side effects of spiral computed tomography for 

lung cancer screening and the role of Pap smears versus Human Papilloma Virus testing for 

cervical cancer screening. 

■ Expand the Cancer Research Network as a population laboratory for evaluating progress in

cancer control and care within integrated health care delivery systems. $0.50 M 

$4.0 M

$10.7 M
NCI’s Challenge 37

■ Collaborate with private and public partners to facilitate transition for obtaining cancer stage

and care data that is not currently part of routine cancer registration. $1.00 M

■ Update linked databases for tracking cancer care, such as the linked SEER-Medicare database,

and develop new linked databases related to cancer control and treatment at the population

level for people under age 65. $0.70 M 

■ Use statistical and methodological research to add to the accuracy and reliability of cancer 

relevant measures — including self-report and various behavioral determinants — for use in 

surveillance and epidemiologic research. $2.00M

■ Develop statistical and graphical methods, software applications, and other technologies 

relevant to geospatial1 and mapping research. $1.00 M

3 . Expand systems and methods to enhance exploration of causes of cancer, generate new

hypotheses on risk, and identify new opportunities for cancer control interventions. 

■ Encourage use of the NCI Atlas of Cancer Mort a l i t y and other population-based data systems. 

■ Provide critical tools for cancer control, especially at the community level in three ways. $2.00 M

■ Develop a Web-based Internet lecture series on use of Geographical Information Systems 

(GIS) and other data sources. 

■ Work with the National Science Foundation on use of geographical data. 

■ Develop software for visualizing disease patterns and advancing use of disease-exposure 

GIS applications. 

■ Support workshops and pilot studies on enhancing surveillance systems for research in geneenvironment interactions and identifying the potential for cancer control interventions at the

population level. $0.50 M

4 . Improve dissemination of information on cancer trends and progress in cancer control and

care to all interested audiences. Enhance training opportunities in surveillance, health

services, and applied research. 

■ Continue to strengthen local and national surveillance data dissemination for research and

health policy planning, applying information technology to boost visual quality, user interaction, and clarity for a diverse audience. $2.00 M

■ Continue the NCI Cancer Pro g ress Report as a vehicle for disseminating summaries of cancer

progress, including new measures and a 2003 feature on dissemination of cancer treatment

advances. $0.50 M

■ Support training of state health department and American Cancer Society personnel in using

surveillance and intervention evidence data in cancer control planning. 

■ Fund existing surveillance and applied research networks and consortia to conduct intensive

training programs, provide sabbatical opportunities for research professionals, and initiate and

develop academic curricula. $1.00 M

Management and Support

To t a l

1 Geospatial is a statistical term referring to information associated with a geographic location, features (such as health care systems), and boundaries (such as cities and states) 

as well as selected attributes. Attributes in this case would refer largely to cancer surveillance data.

$2.5 M

$3.5 M

$2.0 M

$22.7 M
38 The Nation’s Investment in Cancer Research

colorectal cancer screening practices among 2,212

physicians helps identify potential targets for improving compliance with recommended screening. 

A national physician survey on cancer susceptibility

Testing explored comfort with and use of genetic susceptibility testing among 1,250 physicians. 

We have evaluated the use of many new treatment

advances highlighted by successful clinical trials,

NIH consensus development conference reports, and

NCI clinical alerts. For example, patterns of care

studies are drawing from SEER registry data to study

adoption of recommended treatments for breast and

colon cancer. These ongoing studies and the C a n c e r

Care Outcomes Research and Surveillance

C o n s o r t i u m are expected to provide the basis to

evaluate cancer treatments, quality of care, and their

effect on quality of life and other patient-centered

outcomes. We have also supported projects focused

on the economics of cancer and on using claims data

for evaluation of cancer health services.

NCI scientists have also been using modeling to

study the impact of interventions on cancer trends

at state, local, and national levels through support

of the Cancer Intervention and Surveillance

Modeling Network (CISNET) . CISNET mod e ling explores the causes of cancer incidence and mortality trends, analyzes whether recommended interventions are working, predicts the impact of new

interventions, and studies optimal control strategies. 

As requested through state health departments and

American Cancer Society (ACS) divisions, and in

collaboration with the Centers for Disease Control

and Prevention (CDC) and ACS National, we are

building relationships between cancer control planners and CISNET to model the impact of disseminating effective interventions on cancer trends.

We have strengthened our research among cancer survivors, assessing lifestyle and quality of life in

relation to treatment and survival. A seminal workshop co-sponsored by public and private organizations examined the role of physical activity across

the cancer continuum. An NCI-funded study

investigated lifestyle factors among ethnically

diverse breast cancer survivors. 

S P O T L I G H T O N R E S E A R C H

SEER Increases Co verage and Forms Partnerships 

NCI ex p a nded its Surveillanc e, Epide m io l o g y, and End

Results (SEER) pro g ram in 2001 to improve surveillanc e

c o v e ra ge of the full spectrum of the U.S. populatio n .

New covera ge in four states inc reases overall surveill a nce from about 35 million to over 65 million people

a nd improves covera ge of several populatio ns that were

p re v iously unde r re p re s e nted inc l ud i ng ethnic mino r i t ie s,

l o w - i nc o me Whites in rural areas and other areas of

h igh poverty, and re g io ns with high cancer death ra t e s. 

S e v e ral partnership activities with state re g i s t r ie s,

w h ich capture a wealth of info r ma t ion not directly cove red by SEER, have also bro a de ned SEER surveillanc e.

For exa m p l e :

■ NCI, CDC, and the State of Califo r n ia collaborated to

plan specialized cancer cont rol stra t e g ies ge a re d

t o w a rd re duc i ng the local cancer burden. They used

a survey to collect health data and local health syst e ms and policy me a s u res from diverse ethnic,

s o c ial, and cultural commu n i t ies in Califo r n ia. This

s t a nda rdized data can be used in de v e l o p i ng local

c a ncer cont rol pro g ra ms and will allow comparison

with na t io nal cancer cont rol data, pro v id i ng ins ig ht

i nto the dire c t ion of future cancer tre nd s.

■ N CI, CDC, and other partners are working to establish

g u ide l i nes that address the technical diffic u l t ies of

s h a r i ng such as differe nces in the types of data each

registry collects and how the data is store d. Simpler,

s t a nda rdized rules will enable better compara b i l i t y

a mo ng data sets and inc rease opportunity for collabo ra t ion. 

■ NCI is working with others to develop computer

a p p l ic a t io ns that will be able to pool and ana l y z e

data from multiple cancer re g i s t r ies and dissemina t e

t he find i ngs to the cancer commu n i t y. 

T he mo re we can share surveillance data amo ng state

a nd na t io nal age nc ies and the mo re data we can ama s s

t h rough bro a der covera ge of the U.S. population, the

better pic t u re we will have of the cancer burden in the

U.S. and the better equipped we will be to find ways to

re duce that burden. 
NCI’s Challenge 39

To better track emerging trends in cancer and

apply the data to reduce the national cancer burden,

we have been providing new tools for exploring patterns and generating hypotheses for research which

examines the causes of cancer. The G e o g r a p h i c

Information Systems (GIS) for cancer control,

already used for database storage and mapping in conjunction with the Atlas of Cancer Mort a l i t y in the

United States (www. n c i . n i h . g o v / a t l a s p l u s / ), have

been upgraded for use as an analytical tool via two

major additions.2 The Geographic-Based Research

in Cancer Control and Epidemiology, supports use

of the Cancer Atlas and GIS among other a p p l i c ations. A collaboration with the National Science

Foundation supports development for better visualization of data.

Cancer Profiles, an advanced statistical system for

identifying areas in greatest need of cancer control

activities, is being constructed in collaboration with

CDC and other partners. The Web-based design will

allow people who plan, implement, and evaluate cancer control programs to identify regions matching

u s e r-specified comparison criteria. The system will

provide high quality data that relate the effects of

physical and social environments to cancer trends. 

Analytic tool kits, accessible on the Web, make

S E E R and other surveillance databases easier to use

and provide innovative statistical measures as well as

improvements to existing measures.

To communicate and promote the use of important information about cancer trends, NCI has been

improving dissemination and use of data resources

and methods.

NCI is examining the use of workshops to teach

researchers how to use and apply surveillance tools and

data. Topics might include using analytic methods for

complex medical claims data in the S E E R - M e d i c a r e

Linked Database and exploration of innovations in 

statistical methods. 

We are collaborating with public and private partners to organize and streamline data collection, 

statistical methods, and reporting processes. For

example, a major international publishing company

is helping to make a “core engine” that can be used

online to retrieve cancer statistics. The Breast

Cancer Surveillance Consortium and the Breast

Imaging Reporting and Data System Committee of

the American College of Radiology are streamlining

and standardizing data collection instruments and

software systems to enhance the research potential of

national mammography screening data.

NCI published the Cancer Progress Report i n

December of 2001 (progressreport.cancer.gov) to

inform the public, advocates, and other health 

professionals of progress in the Nation’s fight against

c a n c e r, using information drawing on recent 

surveillance research. 

2 While the Atlas of Cancer Mort a l i t y shows geographic patterns of cancer death rates and makes it easy to uncover patterns. GISs provide tools for exploring patterns and 

generating hypotheses.

Cancer Mortality Rates for White Females.

Lung, Trachea, Bronchus, and Pleura. 1970-94

Cancer mortality maps viewed alongside maps showing incidence of smoking can provide clues to researchers working to solve the puzzle of

what causes cancer and its relationship to tobacco use.

Proportion of Women Who Ever Smoked Cigarettes 1992-98
40 The Nation’s Investment in Cancer Research

THE CHALLENGE

A

bout nine million Americans living today have

had a diagnosis of cancer, and another 1.3 million

will be diagnosed in 2001. Of these, a large percentage are undergoing active treatment for their disease,

and all require life-long quality care to detect and

treat recurrences, new cancers, treatment side effects,

and to meet their supportive care needs. In 2001,

direct medical care costs attributable to cancer will

exceed $50 billion. The toll in human pain, suffering, and fear cannot be captured in dollars,

but will be keenly felt by the millions of

people touched by cancer.

The quality of cancer care is a major

national concern. Evidence suggests that

some patients with cancer do not receive

the newer, more effective treatments.

M o r e o v e r, in some cases, there remains

substantial disagreement or uncertainty

about what constitutes optimal care, especially from the patient’s perspective. T h i s

was underscored by reports from the

Institute of Medicine’s National Cancer

Policy Board — Ensuring the Quality of Cancer Care

and I m p roving Palliative Care for Cancer — and by the

P r e s i d e n t ’s Cancer Panel meetings held across the

country to explore why not all Americans get the best

available cancer care. Clearly, too many patients face

significant financial and other barriers to obtaining

appropriate and timely care. But even as society

wrestles with how to make health care more accessible to more people, it is critically important to

advance a comprehensive research agenda that

includes finding ways to improve the quality of the

cancer care, as well as deepening our understanding

of factors that impede access. 

To meet this research challenge, we must: 

■ Define a core set of cancer outcome measures t o

enhance our ability to compare interventions

across studies and over time. Chosen measures

must be patient-centered, acceptable to providers

and payers, span the continuum of care from prevention to treatment and post- treatment care,

including palliative care, and meet the highest

technical standards. 

■ D e f i n e a core set of process measures to identify

those interventions that have been convincingly

shown to improve cancer care outcomes. Process

measures are focused on how care is delivered in

comparison with accepted standards. 

■ Build a stronger data and methods “infrastructure” for conducting quality of care analyses ,

including studies to determine which interventions improve patient-valued outcomes, identify

geographic or racial/ethnic variations in

receipt of quality care, and monitor

quality over time, both at the individual

and population levels.

■ Ensure that therapies shown to be

effective in clinical trials are incorporated into community practice . 

■ Enhance the quality of cancer

c o m m u n i c a t i o n s by gaining a better

understanding of the information needs

of patients, families, and other decision

makers involved in the choice of cancer

interventions. 

PROGRESS TOWARD MEETING THE

C H A L L E N G E

T

he following are examples of some specific

research activities underway related to key elements of NCI’s quality of care research plan.

D eveloping Core Measurements 

Outcome Measures

Identifying clinical and patient-centered endpoint

measures that are valid, reliable, sensitive, and feasible for use in quality of care studies is critical if these

studies are to appropriately inform decision makers.

In response, NCI has convened the C a n c e r

Outcomes Measurement Working Group — 35

internationally recognized experts in measurement,

N C I ’s Challenge: Building Our Capacity for the Future

Quality of Cancer Care

G O A L

Enhance the state o f

the science on the

quality of cancer car e

and inform federal

decision making on

care delivery, courage

and regulation.
NCI’s Challenge 41

o n c o l o g y, and the social sciences — to assess the

strengths and limitations of alternative approaches to

measuring health-related quality of life, economic

burden, and satisfaction with care for the major cancer sites and for every phase of cancer care, and to

make recommendations about core measures for use

across studies. 

A set of papers reviewing and analyzing the published literature in cancer outcomes research over the

past decade will be published as a monograph of the

J o u rnal of the National Cancer Institute in early 2002.

This monograph will critically appraise the current

and potential use of cancer outcome measures across

a broad array of applications — from national level

surveillance, to the evaluation of prevention and

treatment interventions in trials or observational

studies, to monitoring the progress of individual

patients undergoing cancer treatment. The monograph focuses not only on the most prevalent adult

cancers, but also the special challenges in measuring

and monitoring the outcomes of care for childhood

cancer patients and survivors.

P rocess Measure s

For some elements of cancer care, there is such strong

evidence linking provider and health services performance to better outcomes that providing such care

is presumed to enhance quality. Identifying a body of

core process measures of cancer care quality is an

important element for ongoing and future research to

monitor the performance of providers and health systems. To move this effort forward, NCI is working

closely with the National Quality Forum (NQF), created recently to foster voluntary consensus standards

on the quality of health care, focusing on treatment,

survivorship, and palliative care. NCI has actively

collaborated with a number of Federal agencies and

private-sector organizations to assist the NQF in shaping the objectives, agenda, framework, and timeline,

as well as to provide financial and technical assistance.

S t rengthening the Science Base 

N C I ’s Surveillance, Epidemiology, and End Results

(SEER) program , a well known and highly respected

surveillance system, continues to provide a wealth of

information to the private and public research enterprise on the cancer burden, as well as data resources

for assessing the impact of research advances on can

cer outcomes. SEER Pattern of Care Studies a r e

ongoing investigations to monitor the diffusion of

cutting-edge interventions into community practice,

with special attention to population disparities in the

receipt of cancer care. Benchmark studies from 1987

to 1995 on patterns of care for patients with breast

and colorectal cancer will be published in 2001. 

T he Prostate Cancer Outcome Studies ( P C O S ) ,

initiated in 1994, have extended our ability to

understand treatment patterns by collecting information directly from patients and their physicians, as

well as data from medical records, for more than

3,500 men diagnosed with prostate cancer and followed for up to 5 years. Results from a PCOS study

looking at health outcomes after radical prostatectomy or radiotherapy for clinically localized prostate

cancer show that rates of impotence are high among

men receiving radical prostatectomy (79 percent)

and radiation (62 percent). Among the men ages 55

to 59 years, the prostatectomy patients were more

bothered by loss of sexual function than were the

radiotherapy patients. Also, men in the radical

prostatectomy group recovered some urinary and sexual function during the second year after treatment,

while men in the radiotherapy group remained the

same or slightly worse. PCOS results also are providing information on racial and ethnic differences in

advanced-stage prostate cancer. 

The approach of using large cohorts of newly diagnosed cancer patients to study treatment patterns and

monitor the quality of care, has been extended to the

study of colorectal and lung cancers. NCI is providing

support for research teams across the country under

the sponsorship of the Cancer Care Outcomes

Research and Surveillance (CanCORS)

Consortium. C a n C ORS will support the development and application of an expanded set of core

process and outcome measures and will examine

m e t h odological issues in outcomes research conducted in community settings. The potential value of such

large cohort studies for quality assessment is being

increasingly recognized within the oncology commun i t y. For example, the American Society of Clinical

Oncology has launched such a study, focusing o n

breast and colorectal cancer, as part of its National

Initiative on Cancer Care Quality.

Studies linking SEER and Medicare data are also

extremely useful to the research community and

other stakeholders assessing the quality of cancer

care. A study looking at age and adjuvant chemotherapy use following surgery for colon cancer reports that

more than 70 percent of colon cancer patients age

65-74 initiated postoperative chemotherapy during

the period 1991-1996. However, rates of use declined
42 The Nation’s Investment in Cancer Research

THE PLAN — QUALITY OF CANCER CARE

Goal

Enhance the state of the science for defining, measuring, monitoring, and improving the quality

of cancer care, and inform both public- and private- sector decision making on cancer care

d e l i v e r y , coverage, regulation, and standards setting. 

Objective and Milestones for Fiscal Year 2003

1. Develop core process and outcome measures for assessing the quality of cancer care.

■ Support research to improve the theory and practice of patient-centered outcomes measurement in cancer, including the development and testing of new instruments, item banking, and

computer adaptive testing to improve the efficiency and accuracy of data collection as well as

statistical studies to facilitate the “cross-walking” of scores between competing instruments.

$1.50 M

■ Continue to participate in and provide supplemental funding for the National Quality Forum

in order to identify core process measures of cancer care quality. $1.00 M

2. Strengthen the methodological and empirical foundations of quality of cancer care

assessment.

■ Sustain support at $7.5million per year for Cancer Care Outcomes Research and Surveillance

Consortium (CanCORS) studies of dissemination of state-of-the-science therapies and palliative care into community practice, the influence of modifiable risk factors, and disparities in

the delivery of quality cancer care. 

■ Sustain support for Cancer Research Network population laboratories for cancer control

research, with additional emphasis on studies of the quality of cancer care in community settings. (See page 36, Objective 2.) 

■ Sustain support for Surveillance Epidemiology and End Result program (SEER) pattern of care

studies to produce regular and timely information on levels, trends, variations, and dissemination of treatments of proven efficacy and effectiveness. Integrate results from these studies with

Cancer Intervention Surveillance Modeling Network (CISNET) models to predict effects of

treatment dissemination on population trends in cancer survival and mortality. (See page 38.)

■ Increase support for analyses of the SEER-Medicare database to investigate the diffusion and

outcomes of selected cancer interventions. $2.00 M

■ Support the creation of databases that link tumor registry information with private payer

administrative data to expand capacity to investigate whether cancer interventions are reaching and improving the health of individuals under age 65. $2.00 M

■ Continue support for innovative research on economic and health care delivery system determinants of quality of cancer prevention, screening, and treatment services at the community

level. $2.50 M

■ Sponsor new studies to strengthen the methodological foundations of outcomes research and

quality of care assessment. $1.50 M

$2.5 M

$8.0 M
NCI’s Challenge 43

3. Enhance quality of care research within the NCI clinical trials program.

■ Sponsor a symposium and follow-up workshop to bring together leading researchers, patient

advocates, and the relevant Federal agencies to assess the current state of the art, identify key

research questions, and develop a decision strategy for encouraging comprehensive assessment

of patient outcomes for clinical trials. $0.50 M 

■ Using knowledge gleaned from a workshop on the determinants of diffusion of medical innovations, expand support for studies of diffusion patterns and the overall diffusion rates of important clinical trial findings into community practice. $0.50 M 

4. Improve the quality of cancer care by strengthening the quality of cancer

communications. (See Cancer Communications Opportunity, pages 88-92.)

■ Assess the current status of cancer communications. 

■ Support the Centers of Excellence in Cancer Communications Research. 

■ Create new communications products for cancer care decision making. 

■ Convene an interdisciplinary group of scholars, organization gatekeepers, and funders to identify

research strategies and opportunities for collaboration. 

5. Ensu re that the best available scientific evidence about quality measures and assessment

informs Federal decision making on cancer care. Share new knowledge with public and

private partners on ways to translate quality of care research into better medical practice.

Collaborate with these partners to identify core measures of cancer care quality. 

■ Continue to support interagency demonstration projects organized through the Quality of

Cancer Care Committee, a forum for coordinating Federal activities to improve the quality of

cancer care. 

■ Capitalize on the collective clinical and policy expertise of the QCCC to provide technical

assistance and advice to public agencies and private organizations upon request. 

Management and Support

To t a l

$1.0 M

$2.0 M

$0.5 M

$14.0 M
44 The Nation’s Investment in Cancer Research

markedly for older patients, even after adjusting for

measures of comorbidity. Also, African American

patients were found to be less likely to receive

chemotherapy than Whites, even among patients

with no major comorbidities. Further investigation is

necessary to determine whether patient preferences,

physician attitudes, or other factors in the health care

system explain the care patterns. 

In an effort to develop analogous information

and data on patients under 65 years of age, NCI has

been working with managed care systems to promote collaborative cancer research. Through the

Cancer Research Network (CRN) initiative , a

consortium of researchers affiliated with 10 major

n o t - f o r-profit HMOs is conducting studies of latestage breast and invasive cervical cancer cases to

identify patient, provider, and system factors that

affect advanced disease. 

Enhancing Quality of Care Research within

the NCI Clinical Trials Pr o g ra m

The NCI clinical trials program provides an ideal

venue to assess quality of care by incorporating valid,

reliable, quality-of-life endpoints into clinical study

design. NCI staff are working with clinical trials

investigators around the country to assist them in

decisions about the appropriate inclusion of qualityof-life endpoints in NCI-sponsored trials.

I m p roving the Quality of Cancer Care by

S t rengthening Cancer Communications

U l t i m a t e l y, improved cancer care depends on our

ability to translate messages about prevention, treatment, patient care, survivorship, and end-of-life

issues to the research community, providers, patients,

and payers. As part of NCI’s investment in Cancer

Communications as an Extraordinary Opportunity,

several efforts already underway focus directly on the

quality of cancer care. (See pages 89-92.) 

Ensuring the Best Available Scientific

Evidence To Inform F e d e ral Decision

Making on Cancer Care

In 1999, the Department of Health and Human

Services created the Quality of Cancer Care

Committee (QCCC), a trans-agency task force with

representatives from Federal agencies involved in

cancer care delivery, coverage, regulation, and

research. The QCCC, currently chaired by NCI, was

created on the principle that Federal-level decisions

about cancer care should be consistent with the best

scientific evidence available on quality outcomes.

NCI is working directly with:

■ The Department of Veterans Affairs, on the

Quality Enhancement Research Initiative Center,

to promote the use of evidence to foster better

patient outcomes and promote ongoing system

wide improvements in detection and treatment of

colorectal cancer. 

■ The Centers for Medicare and Medicaid

S e r v i c e s , on a project to improve the quality of

cancer care by increasing colorectal cancer

screening rates within the Medicare beneficiary

population and their primary care physicians in

North and South Carolina. 

■ The Health Resources and Services

Administration (HRSA) and the Centers for

Disease Control and Prevention, on a project to

improve cancer screening, referral, and follow-up

in Federally supported primary care health clinics.

One objective of this project is to reduce health

disparities for the underserved population cared

for by HRSA-supported community health centers throughout the United States.

■ The Food and Drug Administration, in an effort

to determine the benefit of selected endpoints,

including clinically oriented and patient-reported

outcomes, to help judge drug efficacy and health

marketing claims. The aim is to understand the

value added — in terms of information important

to patients and other decision makers — from

using measures of health-related quality of life in

addition to, or instead of, symptom-based indicators of patient status and improved survival.
THE CHALLENGE

T

he unequal burden of disease in our society is a

challenge to science and a moral and ethical

dilemma for our Nation. Cancer-related health disparities occur among all people. This is because cancer develops due to a combination of factors related

to genes, individual behaviors, and social and environmental circumstances. The interaction among

these determines who is born healthy, who grows up

h e a l t h y, who sustains health throughout his or her

life, who survives disease, and who maintains a good

quality of life after diagnosis and treatment. 

NCI-supported research has helped

us make enormous strides in understanding how biological and behavioral

factors determine risks for developing

or dying from cancer and how interventions can mod i f y these risks. We

know much less, however, about the

effects of social position, economic status, cultural beliefs and practices, and

e n v i r o n m e n t a l exposures on cancer

risk. Further research is needed for us to

separate myth from reality and explain the relative

importance of these social, cultural, and environmental determinants of cancer, how they interact with

biological and behavioral determinants, and by what

mechanisms they may increase cancer incidence and

mortality and contribute to disparities in cancer incidence, prevention, care, and outcomes.

PROGRESS T OWARD MEETING THE

CHALLENGE

A

s a result of external and internal reviews of cancer

health disparity issues and research programs, NCI

is working in several high priority areas to better understand the relationship between what we know about

cancer care and how and to whom it is provided.

■ NCI-sponsored Special Populations Networks

for Cancer Awareness Research and T r a i n i n g

( S P N s ) were established at 18 research institutions in 2000 to build relationships with community-based programs, foster cancer awareness

activities, increase minority enrollment in clinical

trials, and develop junior biomedical researchers

in minority and underserved communities. 

In the first year of this program, each SPN has

(1) developed new culturally and educationally

appropriate cancer awareness campaigns focused

on African American, Asian American, Pacific

Islander, Latin American, Native American,

and low-income Appalachian white populations

and (2) built collaborative, community-based infrastructures for cancer 

control research. 

Fourteen of the SPNs have worked to

increase the competitiveness of junior

and minority investigator- i n i t i a t e d

research applications submitted for

peer review by participating in developmental research grant programs

sponsored by NCI. 

■ Two new series of cancer patient education materials for low-literacy populations focus on information in two areas important to these groups,

pain management and clinical trials. The clinical

trials series was created specifically for African

American and Native American groups.

■ NCI collaborated with two Minority-Serving

Institutions to increase access to and involvement

in clinical trials by underrepresented populations,

minority researchers, and patients and physic i a n s . NCI provided support for the development

of culturally appropriate patient education materials and for clinical trials data management.

■ NCI is focusing increased attention on how best

to translate research into improved outcomes for

all populations. NCI leadership helped organize

the Department of Health and Human Services

(DHHS) task force on the dissemination of health

promotion and disease prevention interventions.

N C I ’s Challenge: Building Our Capacity for the Future

Reducing Cancer-Related Health Disparities

G O A L

Understand the causes o f

cancer health disparities

and develop effectiv e

interventions to reduce

or eliminate them.

NCI’s Challenge 45
46 The Nation’s Investment in Cancer Research

THE PLAN — REDUCING CANCER-RELATED HEALTH DISPARITIES

Goal

Understand the causes of health disparities in cancer and develop effective interventions to

reduce these disparities.

Objectives and Milestones for Fiscal Year 2003

1. Create and implement a comprehensive plan for NCI activities in health disparities

research, education, training, and health services support.

■ Expand the capacity of the NCI Center to Reduce Cancer Health Disparities to support NCI

health disparities research opportunities. $2.00 M

■ Disseminate findings on the relationship between disparity factors and cancer care including the cost of untreated cancer to society, the cost/benefit of extending Medicare coverage

to cancer patients without insurance, and the influence of the concept of race on scientific

inquiry. $1.50 M

■ Further develop and implement NCI’s integrated low-literacy program by customizing materials

with cultural and language appropriateness for different audience groups. $1.00 M

2. Improve capacity and accelerate knowledge through fundamental cancer control and 

population research. 

■ Establish Centers for Population Health and Cancer to:

■ Expand understanding of the social and environmental determinants of cancer and the 

psychosocial, behavioral, and biologic factors that mediate them.

■ Develop hypotheses for cancer control research at social, institutional, and policy levels.

■ Develop, apply, and evaluate interventions to improve cancer outcomes and reduce 

outcome disparities. $8.00 M

■ Expand epidemiologic investigations to explore racial and ethnic cancer disparities with a

focus on cancers for which these disparities are greatest (e.g., breast, cervix, kidney, prostate).

$1.50 M

■ Support research on the biologic variability in cancer in terms of tumor aggressiveness, differential response to therapy, genetic polymorphism, and psychoneuroimmunologic factors as

mediators of social environment. $2.00 M

■ Build on findings from the Prostate Cancer Outcomes Study to examine risk factors associated

with late-stage disease — lifestyle, biological and clinical characteristics, and access to care —

while accounting for state-of-the-art measures of socioeconomic status. $1.00 M

3. Expand our ability to define and monitor cancer-related health disparities. 

■ Develop new data collection methods for socioeconomic and cultural factors including 

measures, data sources, and data linkage. $1.00 M

■ Examine informed consent provided with prostate cancer screening and treatment in different

age, race-ethnicity, and socioeconomic groups as a measure of quality of care in situations

where there is uncertainty about the efficacy of interventions. $1.00 M

$4.5 M

$12.5 M

$3.5 M
NCI’s Challenge 47

■ Conduct methodological evidence-based research to ensure that survey, epidemiological, and

clinical research involving cancer risk factors exhibits cross-cultural equivalence. $1.00 M

■ Enhance use of the NCI Cancer Progress Report (progressreport.cancer.gov) process to monitor

health disparity reductions and reach Healthy People 2010 goals. $0.50 M

4. Expand cancer control intervention research in prevention, early detection, treatment,

and communications. 

■ Expand the developmental research grant support for the Special Populations Networks for

Cancer Awareness Research and Training program. $2.00 M

■ Collaborate with the Centers for Disease Control and Prevention to support new intervention

research on barriers to screening for women who underuse or never use breast and cervical

screening and on sociocultural determinants in planning, implementing, and evaluating these

interventions. $3.50 M

■ Develop formal affiliations between NCI Cancer Centers and Minority-Serving Institutions.

(See page 26, Objective 1.)

■ Provide supplemental funding to Cancer Centers for health disparities research that will

reduce the heaviest cancer burdens among disadvantaged populations and address disparities

in risk factors, access to prevention interventions (e.g., smoking cessation, dietary change,

physical activity), quality cancer care, and clinical trials. $2.00 M

5. Reduce outcome disparities in special populations by increasing access to state-of-the-art

clinical trials in cancer prevention and treatment. 

■ Expand Clinical Trials Outreach Programs to increase participation by underrepresented populations, establish clinical trials units at minority-serving medical institutions, and strengthen

clinical trials units at minority-based community oncology sites. $3.00 M

■ Increase clinical trials participation by implementing an NCI fellowship training program for

healthcare providers and forums for minority scientist input into the development of clinical

trials that address issues of special importance for minority and special populations. $1.00 M 

■ Use the radiation oncology-based Cancer Disparities Research Program to expand clinical

research infrastructure in communities with disproportionate cancer-related health disparities and

examine novel approaches to more closely link these groups with cancer researchers. $2.50 M

6. Expand the channels for research dissemination and diffusion. 

■ Expand support for advanced training of state health department staff and American Cancer

Society volunteers in best practices for using surveillance and intervention evidence data in

comprehensive cancer control planning. $2.00 M

■ Establish and maintain local and regional partnerships to understand and overcome cancer

control infrastructure barriers that contribute to health disparities. Establish new comprehensive cancer control program initiative with the Washington, D.C. Department of Health.

Develop and demonstrate approaches for bringing the latest interventions in cancer screening,

care, and treatment, including access to clinical trials, to Native American populations

through national and regional Indian health boards, tribal organizations, the Indian Health

Service, and established Native American investigators. $1.50 M

■ Fund supplements to NCI research grants for dissemination of evidence-based interventions

specifically aimed at reducing health disparities. $2.00 M

$7.5 M

$6.5 M

$5.5 M
48 The Nation’s Investment in Cancer Research

7. Expand minority investigator competition for and minority population involvement in

health disparities research. 

■ Recruit two additional minority scientists and physicians to the Cancer Prevention Fellowship

Program to specifically focus on health disparities research. $0.50 M

■ Fund 30 new cancer education grants for the continuing education of healthcare providers,

outreach and education programs in underserved and minority communities, and the accrual

of minority and underserved populations to NCI-sponsored treatment and prevention trials.

$9.00 M

■ Develop community-based participatory research in cancer control through partnerships

among NCI-funded Comprehensive Cancer Centers, Special Populations Networks, and

Minority-Serving Institutions. $1.00 M

■ Further expand underserved and minority-based clinical investigator training under the radiation oncology-based Cancer Disparities Research Program. $0.70 M

Management and Support

To t a l

Through collaboration with the American Cancer

Society (ACS) and the Centers for Disease

Control and Prevention (CDC), NCI has contributed to the training of state health department

staff and volunteers from 17 divisions of ACS in

best practices for using data to improve cancer

control planning. We also have worked with the

CDC to develop a targeted dissemination plan

for evidence-based cancer control interventions

to be included in the Guide to Community

Preventive Services.

NCI has worked with the Agency for Healthcare

Research and Quality and CDC to promote the

adoption of best practices for clinical and public

health approaches to tobacco control. The

Institute is working with the ACS and NCI-funded researchers to disseminate a dietary intervention through faith-based organizations, tested

with NCI 5-A-Day research grant support, and

found to be effective in two studies conducted

among six African American churches in North

Carolina and Georgia. Working with ACS

regional and African American church 

volunteers, NCI is supporting dissemination

research of a unified Body and Soul program in nine

matched pairs of African American churches in

three regions, and ACS will provide sustained support for the intervention.

■ NCI is providing training for new scientists

focused on health disparities through the Cancer

Prevention Fellowship Program and the Special

Population Networks for Cancer Aw a r e n e s s

Research and Training (SPNs). Opportunities for

new scientists include working through the NCIfunded Latin American Cancer Research

Coalition SPN and working closely with investigators in new prevention and control programs

targeted to African American men.

$11.2 M

$1.5 M

$52.7 M
Highlights of Recent Research on Cancer Related Health Disparities

Treatment Disparities for Lung Cancer Related To Surgical Pr a c t i c e s. An NCI-funded study fo u nd that the

lower survival rate amo ng African Ame r ican patie nts with early-stage, no n - s mall-cell lung canc e r, as compare d

with White patie nt s, is largely ex p l a i ned by the lower rate of tre a t me nt through surgery amo ng Afric a n

A me r ic a ns. This study of 10,984 patie nts 65 years of age or olde r, of whom 860 were African Ame r ican and

10,124 were no n - H i s p a n ic White, showed that:

■ T he rate of surgery was 12.7 perc e nt a ge points lower for African Ame r ican patie nts than for White patie nt s

(64.0 perc e nt versus 76.7 perc e nt ).

■ T he 5-year survival rate was also lower for African Ame r ic a ns (26.4 versus 34.1 perc e nt ) .

■ For patie nts who had surge r y, survival was similar for the two ra c ial gro u p s.

■ For patie nts who did not have surge r y, survival was also similar. 

S t udy results suggest that inc reased use of surgery for African Ame r ican patie nts would improve survival. 

Unnecessarily High Cervical Cancer Mortality Must Be A d d ressed. 

R e s e a rch is ne e ded to de t e r m i ne why, despite a thre e - fold re duc t ion in cervical mortality na t io nw ide in the past

50 years, count ies stre t c h i ng from Ma i ne southwest through Appalachia to the Texa s / Mex ico border as well as

in ma ny Southeastern states and in the Cent ral Valley of Califo r n ia have ex p e r ie nced persistently hig her 

c e r v ical cancer mortality ra t e s. To address this 50-year disparity for a cancer from which no woman in this

Na t ion should die, NCI and its na t io nal, state, and local partners are working to: (1) synt hesize re s e a rc h

k no w l e dge, (2) ide ntify core find i ng s, (3) articulate pro g ram and policy optio ns, and (4) disseminate this info rma t ion to Fede ral, state, and local policy ma ke r s. 

HPV Clinical Trials Expected To Help Improve Control of Cervical Cancer.

C o m p re he nsively cont ro l l i ng the hu man papillomavirus (HPV) would virtually eliminate cervical canc e r, whic h

d i s p ro p o r t io nately affects econo m ically and socially disadvant a ged women aro u nd the world. For the past 2

y e a r s, NCI has been fo l l o w i ng the me d ical cond i t ion of mo re than 5,000 women in Gua na c a s t e, Costa Rica, who

a re enrolled in a ra ndomized clinical trial to evaluate HPV DNA testing and visual and automated cytology techniques and de t e r m i ne the optimum strategy for ma na g i ng low-gra de cervical abno r ma l i t ie s. An HPV vaccine

t r ial to compare the efficacy of two vaccines developed by NCI also is underway in Costa Rica. From 15,000 to

20,000 women will be invited to participate in the trial, which is expected to run for the next 8 years.

Cancer Surviv o rship in Minority and Under s e r ved Ad d ressed by Cancer Centers.

I n v e s t igators at NCI-supported Compre he nsive Cancer Centers are using suppleme ntal fund i ng to exa m i ne :

■ T he phy s ical and psycho s o c ial needs of me d ically underserved cancer survivors and/or their fa m i l ie s a nd ho w

t hese needs compare with those fo u nd in cancer survivors and/or their fa m i l ies from majority populatio ns 

■ S o c io c u l t u ral variables that affect cancer survivorship, particularly those that affect quality of life

■ T he na t u re and effectiveness of ex i s t i ng post-tre a t me nt me d ical and support services de s ig ned for canc e r

p a t ie nts from underserved commu n i t ie s

■ T he effectiveness and feasibility of behavio ral me a s u res and int e r v e nt io ns aimed at assessing and re duc i ng secondary phy s ical and psycho l o g ical c o ns e q u e nces for minority or underserved cancer survivors and their fa m i l ie s

See also page 92 for a report on the Digital Divide Pilot Projects initiative through the Cancer Commu n ic a t io ns

E x t ra o rd i nary Opportunity. 

NCI’s Challenge 49
THE CHALLENGE

I

nformatics involves the use of information technology to integrate and make available emerging biomedical information. NCI needs innovative informatics systems to ensure that the flood of information

stemming from scientific discovery is available to those

who need it. For example, the approximately 30,000

genes within the human genome along with millions

of possible variations have been mapped and made

available to cancer researchers. Furthermore, a number of genes can be expressed differently among thousands of different cancers. To add to this information,

the number of drugs targeted to interact with certain

genes and related proteins is multiplying

every day. Other areas of cancer research

are generating a comparable avalanche

of information. NCI’s challenge is to

develop systems to effectively integrate

and share this knowledge. 

We envision meeting this challenge

with a Cancer Informatics Infrastructure

(CII) composed of three interrelated

components. 

■ The first is a knowledge management core that

works to standardize information and data use by all

NCI programs. 

■ The second consists of information technology

tools which link to the core and allow the capture,

analysis, application, and re-use of information. 

■ The third component is the experts from diverse

areas of scientific research, including informatics,

who apply these tools to problem solving in cancer

research and care. 

The CII will create electronic interfaces reaching and

connecting the entire cancer research community.

Strategic partnerships with commercial, academic, and

other governmental groups will broaden the base of

i n t e r o p e r a b l e1tools, data, and infrastructure. Scientists

must broker the application of this infrastructure in all

fields of cancer research. We must ensure that the

infrastructure can evolve to reflect the ever- c h a n g i n g

research landscape and provide for cross-training of scientists who will bridge the gap between the informatics and biomedical research communities. The efficient, comprehensible, and easy access to varied collections of cancer knowledge will dramaically improve

the rapid translation of research observations into clinical and public health interventions.

PROGRESS TOWARD MEETING THE

C H A L L E N G E

T

he NCI has made much progress in

creating and implementing its informatics system. Our progress includes the

following important achievements.

S t a n d a rds-Based Kno w l e d g e

M a n a g e m e n t

N C I ’s Center for Bioinformatics

( N C I C B ) (ncicb.nci.nih.gov) was established in 2001 to ensure that diverse databases can be

used together seamlessly, making data maximally

accessible and easy to use. The Center provides standardized bioinformatics support and integration to

allow for the smooth progression of investigative efforts

from the level of molecular biology and molecular

genetics through pre-clinical animal modeling to the

informed design of clinical trials.

To ensure that the needs of the cancer community

are recognized in the standards-setting process, the

NCICB has joined several national standards groups.

We are building a repository to comprehensively store

the data used by our programs in adherence with the

international standards used by many other Federal

organizations. This keystone effort will ensure that all

data from NCICB supported programs can be easily

50 The Nation’s Investment in Cancer Research

N C I ’s Challenge: Building Our Capacity for the Future

I n formatics and Information Flow

G O A L

Create an informatics

infrastructure that

enhances information

and resource e xchange

among researcher s.

1 In an interoperable system, diverse individual components are made to communicate with one another and to function as a common database.
shared, whether from clinical trials, animal model programs, basic research, or any other discipline. We are

also creating a unified national repository of healthrelated data needed for efficient sharing. Regular seminars keep NCI and the public up to date on developments in informatics techniques, practices, and stand a r d s .

Through the NCICB, NCI has developed and put

into use common data elements — standard ways of

referring to scientific phraseology — for several cancers, and has provided electronic interfaces among our

cancer research communities for information

exchange. For example, the NCI Enterprise

Vocabulary System (EVS) serves our science communities by organizing and translating their respective distinct, but overlapping terminology. One database is

used for translating among vocabularies used in different scientific specialties, and another builds a common vocabulary. Other EVS services support easy,

u s e r-friendly access to diverse collections of cancer

i n f o r m a t i o n .

Four inter-related research initiatives supported by

the NCICB represent key areas of knowledge in cancer

research. The Center supports and integrates the

efforts of these initiatives with one another and with

the larger cancer community. 

■ N C I ’s new clinical trials infrastructure has

increased information sharing among many clinical

trials and with other types of research efforts and

has helped researchers organize and launch clinical

trials faster and run them more efficiently. 

■ The Cancer Genome Anatomy Project (CGAP)

informatics team has made dramatic strides in

making genomic data from the broader scientific

community easily available to cancer researchers

in a format familiar to them, integrating genetics

information not easily accessible elsewhere.

■ The Mouse Models of Human Cancer

Consortium (MMHCC) informatics team h a s

been instrumental in providing critical information

and tools to MMHCC researchers and quickly integrating the results of MMHCC efforts for use by the

cancer community.

■ The Director’s Challenge — Towards a Molecular

Classification of Cancer was issued by the NCI

Director in 1998 to stimulate the use of molecular

technology for classifying tumors based on distinguishing molecular characteristics. The success

of this effort is dependent on NCI’s informatics

tools and the flow of standardized information to

and from other NCI initiatives and the greater

research community.

Cancer Informatics Tools

N C I ’s informatics tools are promoting the efficient

and safe delivery of effective cancer agents to the

American public. Business support tools have been

implemented to streamline procedures and processes

in the clinical trial system . This effort has dramatically reduced the administrative burden on

researchers and permitted stable staffing requirements

in the face of increasing, sometimes doubling, workl o a d s .

NCI has developed informatics tools to ensure

clinical trial safety. Our standardization of business

rules and toxicity terminology has improved reporting and assessment of previously unknown or severe

toxicities from NCI-supplied investigational drugs.

Success was such that the oncology community has

asked that the improvements be applied to non-NCI

cancer agents and to other research areas.

NCI is developing integrated informatics to promote scientific planning. These tools are flexible and

scalable to help databases remain current as new therapies and further advances in cancer biology are discovered. These tools are applied in numerous areas of

research from refining sophisticated cancer agents

based on their mechanisms of action and planning

their clinical use to reallocating staff to areas of scientific importance and recruiting minority participants into clinical trials. 

NCI is focusing on all aspects of software development for scientific management systems . We have

i n t r oduced a process to manage all phases of NCI 

NCI’s Challenge 51
52 The Nation’s Investment in Cancer Research

THE PLAN — INFORMATICS AND INFORMATION FLO W

Goal

Create a cancer informatics infrastructure that enhances information and resource exchange and

integration among researchers working in diverse disciplines, to facilitate the full spectrum of

cancer investigations.

Objectives and Milestones for Fiscal Year 2003

1. Through the NCI Center for Bioinformatics (NCICB), expand NCI’s backbone 

informatics infrastructure to enable support and integration of NCI-supported basic,

clinical, translational, and population research initiatives.

■ Expand the NCICB to provide additional support, enhance integration of data and development of tools emanating from NCI’s Extraordinary Opportunities. Facilitate information

exchange within and between NCI-supported research initiatives. Support the Cancer

Molecular Analysis Project’s specialized bench-to-bedside information integration and display.

$29.00 M (See page 72, Objective 1)

■ Establish a toolbox of open-source2informatics applications and services based on a common set of

operating principles and standards that support NCI’s diverse cancer research activities. $5.00 M

■ Develop a research infrastructure that uses a “standards stack,” assembling common vocabulary,

standard data elements, and information models to further the exchange of all types of cancer

information and data among the cancer community. $5.00 M

■ Expand information technology-based support services to enhance planning, execution, and

communication of the wide-ranging research portfolio supported by NCI. $10.00 M

2 With “open source” software, the computer source code may be copied and/or mod i f i e d .

3 Plug-and-play means that the hardware or software does not have to be configured, but can be used immediately upon installation.

$49.0 M

S P O T L I G H T O N R E S E A R C H

CGAP Is a Gate way to New Exploration and Disco very

NCI’s Cancer Geno me Ana t o my Project (CGAP) was established in

1997 to de t e r m i ne the ge ne ex p re s s ion profiles of no r mal, prec a nc e r, and cancer cells and to pro v ide public access to this

i n fo r ma t ion for all cancer re s e a rc he r s. The project is now prov id i ng a wealth of hu man and mouse ge no m ic data, info r ma t ic s

tools to query and analyze the data, info r ma t ion on me t ho d s,

a nd access to bio l o g ic ma t e r ials developed through the pro j e c t .

With public data and analysis tools, re s e a rc hers can now find “in

s i l ico” answers to bio l o g ical questio ns in a fra c t ion of the time

it used to take in the lab.

R e s e a rc hers have started mining the CGAP databases (at

c g a p . n c i . n i h . g o v) and are discovering new potent ially canc e r -

c a u s i ng ge ne s, ide nt i f y i ng cand idates for molecular targe t i ng

re s e a rch, and he l p i ng to build mic ro a r rays for cancer cell sig nat u re re s e a rch. For exa m p l e :

■ Because cancer is such a complex disease, find i ng the ma ny

c a nc e r - c a u s i ng ge nes involved and unde r s t a nd i ng their ro l e

is cruc ial to de v e l o p i ng new tre a t me nts to combat the dise a s e. Cancer re s e a rc hers in collabora t ion with CGA P, exa mi ned the ex p re s s ion of mo re than 24,000 ge nes in the ox yge n - deprived (hy p ox ic) cells of glio b l a s t o ma mu l t i fo r me, a

form of brain canc e r. They ide nt i f ied ten ge nes believed to

play a sig n i f ic a nt role in allowing this tumor to thrive unde r

hy p ox ic cond i t io ns. Scie ntists are working to find the funct ion of these ge nes with the long-term goal of de v e l o p i ng

t a rgeted inhibitors that may be used in fo r mu l a t io ns agains t

t he canc e r.

■ Until re c ent l y, diffuse large B-cell lympho ma (DLBCL) had

been tra d i t io nally classified as a single canc e r, but patie nt s

s u f f e r i ng from this disease show diverse re s p o nses to
NCI’s Challenge 53

2. Create a community matrix of interoperable data sources, analytic tools, and 

computational resources that provide an extensible plug- and- play 3informatics 

capability for the cancer research community .

■ Expand the informatics capacity of the larger cancer research community with partnerships to

develop a standards-compliant infrastructure that can be used readily in conjunction with NCI

applications and each partner’s information systems. Establish a minimum of five academic,

government, and commercial strategic partnerships in a research park setting where all partners

can work together to address bioinformatics questions. $15.00 M

■ Use a minimum of 20 investigator-based awards that build on the NCI informatics backbone to

1) deploy the standards-based resources to the cancer research community to serve as the foundation for additional infrastructure and 2) facilitate rapid deployment of related new research 

initiatives. $10.00 M

3. Expand the cancer research community’s capacity to perform informatics research on a

local institutional basis.

■ Establish a network of bioinformatics research centers to work with and through the NIH

Biomedical Informatics Science and Technology Initiative, using a novel interdisciplinary

management team to select and coordinate the centers. $5.00 M

■ Expand standards-compliant institutional infrastructure by providing infrastructure supplements

to NCI-supported research organizations, supporting the growing need of investigator- i n i t i a t e d

research to access state-of-the-art biocomputing tools and data. $10.00 M

■ Promote informatics training by encouraging recruitment of new scientists and cross training in a

variety of life science research domains through 20 development and transition awards. $3.00 M 

Management and Support

To t a l

$25.0 M

$18.0 M

$3.0 M

$95.0 M

c he mo t he ra p y. Only 40% of patie nts re s p o nd well to tre a tme nt, while the re ma i nder succumb quickly to the disease.

Us i ng CGAP data, NCI and NCI-supported scie ntists de v e lo p e d a mic ro a r ray called a l y m p h o c h i p that cont a i ne d

18,000 ge ne s, which inc l uded those pre f e re nt ially ex p re s s e d

in lympho id cells as well as in cancer and the immu ne system. The ex p re s s ion analysis showed that DLBCL can be cate gorized into two distinct classes that broadly corre l a t e

with the clinical outco me s.

T hese results have alre a dy begun to contribute to our goal to

i m p rove de t e c t ion, dia g nosis and tre a t me nt of canc e r. Sinc e

t hese discoveries come from early applic a t ion of CGAP re s o u rc e s,

C GAP’s impact on the future of cancer re s e a rch and clinic a l

a d v a nces promises to be substant ia l .

s oftware development from start to finish. This project maximizes the effectiveness of the spectrum of

NCI resources, including information flow, human

resources, grant management, and space management.

Informatics for Cancer Research and Car e

N e t - Tr i a l sT M is a Web-based clinical trials information system that supports every aspect of the trial,

including information management, data analysis,

and secure Internet access allowing real-time c o l l a boration of multiple centers. Net-Tr i a l sT M s t r e a m l i n e s

operations and improves data quality, patient safety

monitoring, and analysis of much larger groups of

data across the entire clinical trials portfolio. Still

under development, Net-Tr i a l sT M is being used by at

least six clinical branches of NCI’s Center for Cancer

Research and has been piloted at several sites outside

N C I ’s intramural program. 
THE CHALLENGE

T

raining and career development for the next generation of scientists remains one of our most

important challenges. The scientists of the future

will need to be more versatile in their use of new

technologies, able to work in teams to understand the

complicated environmental, lifestyle, genetic, and

molecular variables contributing to human cancers,

and better prepared to translate discoveries into public benefit. We need to implement and sustain multiple long-term strategies to attract the

most talented individuals to cancer

research. We need to create a stable

cadre of well trained technical, biological, behavioral, medical, and public

health scientists dedicated to the cancer research enterprise, who can and

will work together. 

Our success will depend on our ability to move beyond traditional educational and research cultures, overcome

health financing constraints, and

address socioeconomic inequities that have proven to

be barriers to progress in the past. The theme for the

future is to train scientists to work on problems as

integrated, multidisciplinary teams. 

To meet these challenges, we must continue to

implement training and career development strategies to address a number of crucial issues. 

■ We need to more adequately prepare basic scientists and offer them more attractive career paths

by providing the background to conduct cancer

research and preparing them to collaborate on

multidisciplinary research teams. Increasing

trainees stipends to levels more reflective of their

education and skills will help ensure that careers

in basic science will continue to remain attractive. 

■ It is critical that we reverse the migration of talented and creative physicians from research to

practice. This is the single most threatening consequence to cancer research from the shifting economics of the health care system. We need to use

more effective means to train clinical investigators and ensure they have protected time to conduct research that will translate basic discoveries

into better methods for cancer prevention, diagnosis, and treatment. Intensive training and education are necessary to guarantee informed consent and provide maximum safety for patients participating in research.

■ We need to increase the numbers and stabilize

the careers of cancer prevention, control, population, behavioral, and public health scientists.

The discoveries of scientists dedicated to

prevention, early detection, behavior

m odification, and risk factor analysis will

have a major impact on reducing future

cancer incidence and mortality. We

must develop better ways to train these

scientists to function in interdisciplinary

research settings and work effectively

with patient-oriented and basic scientists. We also must provide these scientists with protected time in which to

conduct research. 

■ We need a research community that is ethnically and racially diverse. These scientists must be

sensitive to the factors that lead to disproportionate cancer incidence and mortality and prepared

to conduct research to help overcome the cultural and socioeconomic barriers responsible for the

unequal burden of cancer. 

■ We must attract and integrate technical and

informatics experts into cancer research.

Specialists in these disciplines will provide a critical driving force for future progress.

PROGRESS T OWARD MEETING THE

CHALLENGE

T

he NCI is employing a variety of individual and

institutional training and career development

awards to meet the needs of new and established

investigators and NCI’s anticipated research priori54 The Nation’s Investment in Cancer Research

N C I ’s Challenge: Building Our Capacity for the Future

Cancer Research Training and Career Dev e l o p m e n t

G O A L

Prepare a stable, diverse

cadre of scientists to

work together and use 

technologies for building 

knowledge and translat -

ing disco veries into 

application.
ties. We have focused increased resources on career

tracks for M.D.s in cancer research, behavioral and

population scientists, minority scientists, and scientists in highly technical fields important to the future

of cancer research. 

N C I gives individual awards to scientists at various stages in their careers. 

■ Individual National Research Service A w a r d s c o ntinue to provide a stable cadre of well trained basic

scientists. Many of the awards NCI makes through

this program are for postdoctoral fellowships, which

allow new Ph.D.s an opportunity to begin the transition to becoming independent investigators. 

■ Individual mentored 5-year awards provide special

opportunities for M.D.s in basic or clinical research

and for individuals pursuing cancer prevention,

control, behavioral, and population science.

Interest in these awards has increased dramatically

over the last 2 years, resulting in a three-fold

increase in the number granted – evidence of both

the need for and effectiveness of these programs.

■ Bridging awards encourage basic and minority

scientists to pursue careers in cancer research.

These awards require recipients to undertake

mentored and independent research, providing

them protected time to develop independent

research programs. These special bridging awards

have increased steadily since their inception 5

years ago and are on target for achieving their

strategic objectives.

■ Transition awards provide for 3 years of protected

time for people completing mentored postdoctoral training or for new investigators to initiate successful research programs. These awards are now

in place for NCI’s two most critical areas of need:

M D ’s in basic and clinical research and population

scientists. A new transition award is now available for minority scientists. Because we have not

been able to achieve our targeted objectives for

these awards during their first few years, we are

taking new measures to increase their accessibility

and attractiveness.

■ Established investigator awards provide seasoned

investigators in the clinical sciences and in cancer

prevention, control, behavioral, and population sciences protected time to conduct research and mentor new scientists. The number of these awards has

increased since their introduction, and their availability appears to be helping to curtail the migration

of physicians from research to patient care. 

■ New diversified sciences career development

a w a r d s attract technology developers and scientists in disciplines not traditionally associated with

cancer research but clearly needed for the future.

Institutional awards are 5-year awards for developing

and conducting training and career development programs. These awards achieve special goals by establishing specific requirements and assembling mentors

whose skills support program objectives.

■ National Research Service A w a r d s , NCI’s mainstay for training basic scientists, include special

provisions for curricula and research environments that expose all trainees to cancer- r e l a t e d

opportunities and important new research

approaches of the future.

■ Institutional Clinical Oncology Career

Development Programs prepare the next generation of clinical scientists to design and implement

hypothesis-based clinical trials and to collaborate

with basic scientists. There are now nearly 20 of

these programs in place throughout the nation.

■ Institutional Education and Career Development

P r o g r a m s , initiated in 2000, prepare participants

for multidisciplinary team research settings. This

program is proving to be extremely successful in

stimulating new, forward-looking training programs in prevention and control, imaging sciences,

outcomes research, and molecular pathology.

■ The Continuing Umbrella of Research

Experiences Program engages minority high

school and undergraduate students and provides

them with assistance through all stages of training

and career development needed to become independent investigators. 

■ M i n o r i t y Institution/Cancer Center Partnerships

have the potential to link over 300 MinorityS e r ving Institutions1 with NCI Cancer Centers to

increase the number of minority students in cancer research; strengthen the research capabilities

of minority institutions; reduce cancer incidence

and mortality in minority populations. Several

comprehensive partnerships are now operating,

and many are in the planning stages. 

For more information on these programs and career

tracks, go to cancer.gov/cancertraining. 

NCI’s Challenge 55

1 Colleges and universities whose enrollments include a significant proportion of students from minority groups that are underrepresented in science
56 The Nation’s Investment in Cancer Research

THE PLAN — CANCER RESEARCH TRAINING AND CAREER

DEVELOPMENT

Goal

Build a stable, racially and ethnically diverse cadre of basic, clinical, behavioral, and population

scientists trained to work together effectively and to use the most advanced technologies in

building our knowledge base and in translating discoveries into more effective cancer prevention, detection, diagnosis, and treatment strategies.

Objectives and Milestones for Fiscal Year 2003

1. Continue to provide training, career development opportunities, and protected research

time to developing and established cancer scientists. 

■ Maintain a stable National Research Service Award (NRSA) program to train pre-doctoral and

post-doctoral basic scientists through traditional institutional and individual awards. Increase the

stipends of trainees by 10 percent in order to make research careers more attractive. $3.00 M

■ Continue to increase the participation of clinically trained individuals in basic and in patientoriented research by funding 20 new individual mentored awards, 20 new transition awards,

and 10 new established investigator awards. $7.00 M

■ Expand the number of well trained population, behavioral, and public health scientists in cancer research by funding 20 new individual mentored awards, 15 transition awards for junior

independent scientists, and 10 awards to established investigators. $5.00 M

■ Expand the role of the NCI Intramural Program in training extramural investigators by funding

five additional trainees in the NCI Scholars Program and by creating two new intramural

training and career development programs that partner and network with extramural institutions and focus on underdeveloped areas that can benefit by integrating sparse resources (e.g.,

radiation oncology, informatics, prevention). $3.00 M 

2 . Continue to provide and refine special training and career development opportunities that

prepare new and established scientists to function in collaborative, team research settings

and that integrate new technical disciplines into the cancer research enterprise.

■ Increase the number of basic scientists who focus on human cancer research and who can collaborate effectively with clinical and population scientists in translational research by funding

30 new special bridging career awards. $4.00 M

■ Fund five new Institutional Clinical Oncology Career Development Programs to prepare clinically trained individuals to become expert in all aspects of clinical trials design and implementation as well as effective partners of basic scientists in moving discoveries in the laboratory to

improved clinical tests and therapies. $3.00 M

■ Implement 10 new Institutional Career Development Programs for training scientists for highly

complex interdisciplinary team research settings. $5.00 M 

$18.0 M

$18.0 M
NCI’s Challenge 57

■ Support five new individual Diversified Sciences Career Development Awards to attract

new disciplines (e.g., physics, engineering, informatics) into multidisciplinary cancer

research settings. $1.00 M 

■ Expand and initiate career development opportunities in highly specialized interactive, translational, and research consortia and networks (e.g., Specialized Programs of Research Excellence,

Imaging Centers, Tobacco and Tobacco-Related Centers) that are accessible to new and established investigators. $5.00 M

3. Expand programs to recruit, train, and sustain underserved racial and ethnic minority

individuals in cancer research and provide partnership opportunities for training and

career development.

■ Expand the Continuing Umbrella of Research Experiences (CURE) Program by: adding 50

trainee positions on institutional NSRAs; providing new supplemental funding to 10 cancer

centers for high school and undergraduate student research experience; adding 10 minority

training positions in Clinical Oncology Career Development Programs; funding 10 new positions for Cancer Education and Career Development Programs in the population sciences;

funding 50 new Minority Investigator Supplements to NCI research project grants; funding 20

new mentored career development awards for basic and clinically trained scientists; and funding 10 new Career Transition Awards for basic, clinical, behavioral, and population minority

scientists in their first junior faculty positions. $15.00 M

■ Promote collaborations between scientists and educators in MSIs and in NCI-designated Cancer

Centers through 15 planning grants for developing MSI/Cancer Center research training programs for minorities and outreach education programs for minority communities. $3.00 M

■ Increase minority access to training and career development opportunities by improving NCI

Internet information services, establishing linkages between public and private agencies that

provide related services, and establishing 20 new positions in NCI Cancer Centers that will

“broker” the connections between minority individuals seeking research experiences and

Cancer Center scientists. $2.00 M

■ Integrate the NCI CURE and Minority Institution/Cancer Center Partnership Programs more

effectively into the Minority Biomedical Support Grant Program in the National Institute of

General Medical Sciences. 

Management and Support

To t a l

$20.0 M

$2.0 M

$58.0 M
58 The Nation’s Investment in Cancer Research

An i mal mo dels — laboratory animals that have specific

c h a ra c t e r i s t ics re s e m b l i ng a hu man disease or disorder —

play an invaluable role in cancer re s e a rch. Te c h no l o g ie s

available today allow scie ntists to create animal mo dels of

c a ncer by tra ns f e r r i ng new ge nes into animals or ina c t i v a ti ng certain ex i s t i ng ge ne s. This ma kes the animals susceptible to specific cancers via the same ge ne t ic and enviro nme ntal factors that affect hu ma ns. With these mo de l s, scie ntists can study the bio l o g ical changes associated with

every stage of tumor de v e l o p me nt, test new appro a c hes to

de t e c t ion and dia g no s i s, and evaluate pre v e nt ion and tre a tme nt stra t e g ie s. 

For a variety of re a s o ns, mice are particularly well suited

for cancer re s e a rch. To start, mice and hu ma ns are similar

in their ge ne t ic ma keup and susceptibility to canc e r. As a

result, the de v e l o p me nt of tumors in mice largely para l l e l s

that in hu ma ns. Furthe r, mouse tumors develop over the

course of mo nt hs ra t her than the years usually re q u i red fo r

c a ncer to develop in larger animals and hu ma ns. 

But the complexity of cancer ma kes the de v e l o p me nt of

mouse mo dels a far mo re challeng i ng task for cancer than

for some other diseases. Fortuna t e l y, cancer re s e a rc he r s

t o day have a wide ra nge of re s o u rces to bring to bear on

this task. Scie ntists have access to inc re a s i ngly de t a i l e d

databases cont a i n i ng the details of mouse and hu ma n

ge nes and a gro w i ng body of info r ma t ion on the mo l e c u l a r

c h a ra c t e r i s t ic s, or s i g n a t u r e s, of tumo r s. This ex p a nd i ng

k no w l e dge – coupled with tools for mo d i f y i ng the ge nes of

l a b o ratory mice and a battery of tests to ide ntify re l e v a nt

c a ncer ge nes and pro t e i ns – ens u re that cancer mouse mo dels parallel the de v e l o p me nt, pro g re s s ion, and clinic a l

course of hu man canc e r s. 

To improve the pace and effic ie ncy with which mo u s e

mo dels of cancer are developed and tested, and to ens u re

t hey are readily available to scie nt i s t s, NCI created the

Mouse Models of Human Cancers Consortium in late

1999 by fund i ng 20 mu l t id i s c i p l i nary groups of investig at o r s. Consortium scie ntists are working to develop and

e v a l uate mouse mo dels for breast, pro s t a t e, lung, ovary,

cervix, panc re a s, skin, blood and lymph system, colon, and

b rain canc e r s. 

H ow Mouse Models Are A d vancing Cancer

R e s e a rc h

Th ro u g hout the Consortium and in other NCI-supported labo ra t o r ie s, re s e a rc hers are using mouse mo dels to do the fo ll o w i ng: exa m i ne the interplay of ge ne t ic and enviro n me nt a l

factors in cancer susceptibility; test novel appro a c hes to

de t e c t ion, dia g no s i s, and ima g i ng; and advance the use of

ge ne t ically eng i ne e red mice for pre v e nt ion, the ra p y, and

p o p u l a t ion re s e a rch. 

Mouse mo dels pro v ide a unique opportunity to ex p l o re

h ow genetic and environmental f a c t o rs inter a c t to give

rise to canc e r. With such mo de l s, scie ntists can test the

effects of a particular che m ical in a cont rolled enviro n me nt

u s i ng animals with a known ge ne t ic ma keup. For exa m p l e,

re s e a rc hers are using a re c e ntly developed mouse mo del of

l u ng cancer to investigate the role that ge ne t ic factors play

in de t e r m i n i ng why some smo kers develop lung cancer and

o t hers do not. The mo del also is being used to test

w he t her tobacco smo ke accelerates tumor fo r ma t ion, and to

de f i ne the ge nes that confer susceptibility to tobaccorelated canc e r s. 

Because samples of hu man cancers at their earlie s t

s t a ges can be difficult to obtain, mouse mo dels also are

i n valuable in cancer detection studies . Tu mors in the s e

m ice can be exa m i ned to verify the role that each ge ne t ic

a l t e ra t ion plays in causing cancer and in its pro g re s s ion, and

may also reveal changes info r mative to hu man cancer dia gnosis or early de t e c t ion. An example of this type of

re s e a rch is a newly developed mouse mo del that closely

m i m ics inflammatory bowel disease, a cond i t ion associa t e d

with inc reased cancer risk. Researc hers are using this mo de l

to test the effect of known and suspected causal factors –

s uch as the He l icobacter bacteria – on the timing and severity of canc e r. By taking bio p s ies at varying times after

i n f e c t ion, they are looking for the earliest changes ind ic a ti ng inc reased risk for gastric, int e s t i nal, or colon canc e r. 

S P O T L I G H T O N R E S E A R C H

Mouse Models of Human Cancers Consortium — 

Modeling Human Cancers in the Mouse
D e f i n i ng the changes associated with cancer is fundame ntal for successful early de t e c t ion, as well as for find i ng

p o t e nt ial targets for early int e r v e nt ion. Once these targe t s

have been ide nt i f ie d, scie ntists de p e nd on mouse mo dels to

test the e f f i c a c y of new drugs , and to u n d e rstand why a

drug does — or does not — work as e x p e c t e d. Inde e d,

o ne of the most important roles of mouse mo dels is in the

de v e l o p me nt of drugs to treat canc e r. 

In one re c e nt example of using mouse mo dels to t e s t

t re a t m e n t s , investigators used a mo del of one type of childhood leuke m ia to help solve the mystery of why some children re s p o nd to the standa rd the rapy of re t i no ids while others do not. As they stud ied the problem in the mo del, scie ntists discovered that the mice that did not re s p o nd to tre a tme nt had an unexpected ge ne re a r ra nge me nt. With this

i n fo r ma t ion, the re s e a rc hers then developed a new tre a t me nt

that blocks the action of the re a r ra nged ge ne. It was effective in combina t ion with re t i no ids in mic e, and these invest igators are now assessing the combined tre a t me nt in childhood leuke m ia patie nts who do not re s p o nd to re t i no id the rapy alone. Mo dels also are valuable for studying a host of

t reatment questions , such as de t e r m i n i ng me c h a n i s ms of

drug re s i s t a nce and de f i n i ng new tre a t me nt targe t s. 

With specialized equipme nt and techniques for ima g i ng

m ice and other small anima l s, investigators are using mo u s e

mo dels to ex p l o re improvements in cancer imaging and

t re a t m e n t in order to de t e r m i ne whe t her ant i - c a ncer dr u g s

have re a c hed their targets and to track re s p o nse to the ra p y.

S i nce 1999, much of this re s e a rch has been fo s t e red by

S mall Animal Ima g i ng Resource Pro g ra ms that NCI has establ i s hed at a number of re s e a rch centers aro u nd the count r y.

(See page 67 for mo re info r ma t io n . )

As Consortium investigators develop mo re mouse mo de l s

of canc e r, collabora t io ns between them and small anima l

i ma g i ng specialists are expected to gro w. Alre a dy,

C o nsortium scie ntists involved in de v e l o p i ng mouse mo de l s

for prostate cancer have teamed with colleagues from the

N C I - f u nded Small Animal Ima g i ng Resource Pro g ram to use

p o s i t ron emission tomo g ra p hy ima g i ng to study pro s t a t e

c a ncer de v e l o p me nt, from its beginnings in the prostate to

its metastasis (spread) to bones and other org a ns. Similarly,

i n v e s t igators testing mouse mo dels of brain tumors are coll a b o ra t i ng with small animal ima g i ng experts to use ma g ne tic re s o na nce ima g i ng to test appro a c hes to ge ne the rapy fo r

b rain tumo r s. Experime nts of this kind are alre a dy re v e a l i ng

new avenues for hu man the ra p y. 

The Future of Mouse Models

If the re s e a rch community is to employ mouse mo dels to

t heir greatest advant a ge, ex t e nsive collabora t io ns are ne e de d

a mo ng those who can best inform the de s ign of the mo de l s

a nd their ultimate use in cancer re s e a rch. NCI is fa c i l i t a t i ng

t he fo r ma t ion of collaborative groups — e.g., for ovaria n ,

b rain, pedia t r ic, and panc re a t ic cancer mo de l i ng — to

e ns u re ra p id inc o r p o ra t ion of hu man cancer re s e a rch discove r ies into mouse mo del de s ign and applic a t ion. With NCI’s

help to organize confere nces and symposia, Cons o r t i u m

i n v e s t igators are spearhe a d i ng the dissemina t ion of info r mat ion about mouse eng i ne e r i ng tactic s, de v e l o p me nt of valida t ion standa rds for cancer mo de l s, and the pra c t ical applic a t ion of mo dels to inform ma ny aspects of cancer re s e a rch. 

T he achie v e me nts of Consortium investigators and the

need to deploy mo dels to the re s e a rch community pro m p t e d

NCI to establish the Mouse Mo dels of Hu man Canc e r s

C o nsortium Mouse Repository (web. nc i fc r f . go v / re s e a rc h res o u rc e s / m m h c c / de fault.asp), to which int e rested scie nt i s t s

a re invited to contribute mo de l s. When it opened in

F e b r uary 2001, the NCI repository had three mouse stra i ns

available for distribution. The number of mouse mo de l s

of f e red is expected to quickly inc re a s e, re a c h i ng at least 30

by early 2002. NCI will ex p a nd the repository in the future

to accommo date the gro w i ng re q u i re me nts of the canc e r

re s e a rch community for well-de s ig ned and tho roughly tested

mouse mo de l s. For mo re info r ma t ion about Consortium prog ra ms and pro j e c t s, and access to its da t a b a s e s, go to

m m h c c. nc i . n i h . go v. 

Mouse Models 59
Extraordinary Opportunities

for Investment

60 The Nation’s Investment in Cancer Research

Extraordinary Opportunities 

2003 Budget Increase Request

(dollars in thousands)

Genes and Environment $55,500

Cancer Imaging 69,800

Defining the Signatures of

Cancer Cells 75,000

Molecular Targets of Prevention 

and Treatment 42,500

Research on Tobacco and

Tobacco-Related Cancers 67,000

Cancer Communications 19,050

Total $328,850

Defining the Signatures

of Cancer Cells 22.8%

Cancer Communications

5.8%

Research on TobaccoRelated Cancer 20.4%

Molecular Targets

of Prevention and

Treatment 12.9%

Cancer Imaging 21.2%

Genes and the

Environment 16.9%

T

he NCI’s “extraordinary opportunities for

investment” are broad-based, overarching areas

of scientific pursuit that hold tremendous promise for significantly expanding our understanding of

c a n c e r. With focused efforts and increased resources

in these areas, we can build on past successes and

technological breakthroughs to stimulate dramatic

progress in addressing some of our most difficult questions. Although the needed resources are not trivial,

our failure to respond quickly with investment in all

of these areas will slow the pace of cancer research at

all levels and impair our ability to find better ways to

care for those whose lives are touched by cancer. 

NCI seeks formal input from cancer experts representing a broad spectrum of perspectives to help identify these areas of exceptional promise. Every three

years, we ask members of the research community,

advisory groups, and advocacy organizations to revisit the “extraordinary opportunities” and recommend

important areas of research into which additional

resources should be infused over the next three-year

cycle. We thoroughly assess these responses, blend

related ideas, and, with our advisors, select new

investment areas. The current six extraordinary

opportunities were first outlined in NCI’s Fiscal Ye a r

2001 budget proposal and are continued in this proposal for Fiscal Year 2003. 

The purpose of the extraordinary opportunities is

to identify areas of discovery that build upon important recent developments in knowledge and technology and that hold promise for making significant

progress against all cancers. Extraordinary opportunities must involve approaches to cancer research

beyond the size, scope, and funding of our current

research activities, be implementable with specific

defined investments, and be described in terms of

achievable milestones.

The plans proposed for these extraordinary opportunity areas describe new research awards and new or

expanded programs and collaborations intended to

help improve the prospects for patients and survivors

of all types of cancers.
THE OPPORTUNITY

A

s we better understand the interplay between

inherited susceptibility to cancer and environmental risk factors, we will be able to develop more

meaningful approaches to cancer prevention, early

detection, and treatment. Until recently, we have

pursued separate lines of inquiry for cancer genetics

and environmental risk factors for cancer. As such, we

have been able to identify some of the human genes

that make people susceptible to cancer, to apply

increasingly sophisticated molecular technologies to

analyze genetic changes, and to examine the relationship between disease development and individual

genetic profiles. We have learned about

a variety of carcinogenic environmental

factors not only in the outdoors but also

in the home and workplace. These

include pollutants in air, water, and soil;

components of food, tobacco, alcohol,

and drugs; sunlight and other forms of

radiation; and infectious agents. 

Early efforts to discover how genes

and environmental factors interact to

cause cancer are showing promise but

also highlight the complexity of the

puzzle. Some genes have proven to be

so powerful that their presence in an

individual makes cancer highly predictable. For

example, carriers of the gene for Familial

Adenomatous Polyposis are almost certain to develop

colon cancer. But an inherited predisposition to

other types of cancer requires other factors for cancer

to occur, such as the presence of other genes or exposures to chemicals in the environment. For example,

mutations in the susceptibility genes BRCA1 and

BRCA2 are risk factors for breast cancer that may be

related to a combination of factors. Similarly, some

environmental exposures — tobacco use, for example

— can be strong, but not certain, predictors of cancer. 

N C I ’s opportunity is to uncover elements of the

gene-environment interaction that can lead to tangible improvements in our ability to prevent and control cancer. For example, we expect to identify previously unsuspected carcinogens through the study of

newly discovered genes that predispose people to canc e r. We also want to learn how certain environmental exposures increase the cancer risk for genetically

susceptible subgroups. When we can define the cancer risks associated with specific environmental and

genetic factors and their interactions, we can develop

new individual and public health strategies to avoid

adverse exposures, check genetic susceptibility earlier,

identify appropriate treatment regimes, and take special precautions for people at high risk. 

To progress in this area, NCI needs to develop new

ways to study cancer genetics, environmental exposures, and their interaction and to maximize the availability and use of large

amounts of research data and other

resources. Large-scale studies that

require new levels of cooperation and

innovation from the cancer community

will be needed to achieve tangible

improvements in medical practice and

public health. 

PROGRESS IN PURSUIT OF

OUR GOAL

T

he NCI is pursuing research opportunities in five

growth areas to better understand cancer- r e l a t e d

genes, environmental factors, and their interaction.

First, we are building the capacity to understand

genetic variation, identify important biologic exposures, and explore the complex interaction among

them through research collaborations with many

p a r t n e r s .

■ I n v e s t igators already involved in 15 separate

prospective studies of large population groups are

pooling high quality environmental exposure data

along with tissue, blood, and other body fluid samples suitable for genetic analysis to form a combined

study size of 700,000 participants, large enough to

yield significant findings. Some members of this

Extraordinary Opportunities 61

1

E x t ra o r dinary Opportunities for Inv e s t m e n t

Genes and the Envir o n m e n t

G O A L

Disco ver genetic ,

environmental, and 

lifestyle factor s

and their interactions 

that define cancer 

risk and inform 

strategies for 

cancer control.
62 The Nation’s Investment in Cancer Research

THE PLAN – GENES AND THE ENVIRONMENT

Goal

Discover genetic, environmental, and life style factors and their interactions that define cancer

risk and that can inform the development of new strategies for prevention, early detection, and

t r e a t m e n t .

Objectives and Milestones for Fiscal Year 2003

1. Identify new environmental risk factors and susceptibility genes and determine their

interactions in cancer causation. 

■ Utilize the unique advantages of the Cohort Consortium to investigate exposures best studied in

large populations and their interactions with susceptibility genes.

■ Continue the five-center gene-environment risk factor discovery study of breast and 

prostate cancers while adding studies of other common cancer sites. $3.00 M

■ Expand the number of participants, population diversity, and types of biospecimens. $2.00 M

■ Support Case-Control Consortium investigators to address specific gene-environment interactions in detail. Establish formal resources for discovery efforts by initiating large populationbased and hospital-based studies to develop comprehensive data and specimen resources by cancer site. Encourage use of the NCI Atlas of Cancer Mortality and other public use data systems

(e.g. Long Island Breast Cancer Study) as source of study from high risk areas. $4.00 M.

■ Continue improving infrastructure to meet the needs of large, collaborative human 

population studies. 

■ Maximize the utility of specimen resources for human population studies with improved 

efficiency and cost-effectiveness of specimen collection, processing, storage techniques, and 

high-throughput assays. $2.00 M

■ Continue developing informatics systems to capture, store, analyze and integrate the 

massive amount of information generated by these studies. $3.00 M

■ Facilitate the use of new genomic technologies by funding supplements to existing 

gene-environment focused studies. $2.00 M

2. Develop new ways to assess and measure environmental exposures for use in population

studies. 

■ Support development of new methods for characterization of internal dose resulting from 

complex lifetime exposures. $2.00 M

■ Continue expanding NCI’s Innovative Molecular Analysis Technologies Program to develop

new non-invasive techniques for collecting and measuring DNA and proteins in very small

amounts of biologic material. $2.00 M

■ Continue support for applying and validating measures of the cumulative cellular, genetic, and

molecular effects of environmental exposure through funding supplements for ongoing research

programs. $2.00 M

3. Identify cancer-predisposing genes in high-risk families and investigate how other genes

and environmental factors modify expression of these genes. 

■ Fund two new consortia of investigators to identify unknown cancer susceptibility genes 

(e.g., pancreatic cancer). $4.00 M

$16.0 M

$6.0 M

$8.0 M
Extraordinary Opportunities 63

■ Support interdisciplinary studies for gene discovery and characterization for additional cancer

sites by new collaborative family registry groups. $2.00 M

■ Support collection of fresh-frozen tumor tissue and other biospecimens from genetically cancerprone families for microarray-based molecular signature analyses in NCI-supported large population research resources such as a Cancer Family Registry Web site. $2.00 M 

4. Develop tools for the study of gene and environment interactions in human populations. 

■ Extend the Genetic Annotation Initiative to identify new gene variants relevant to cancer in

clinically and epidemiologically defined populations, and for various molecular applications. (See

page 72, Objective 1.)

■ Augment the Mouse Models of Human Cancers Consortium to more rapidly localize interesting

genetic regions, increase the number of models for human hereditary cancer genes, decipher

environmental factors that modify cancer development, and test biomarkers for early detection.

$2.50 M

■ Provide the framework for productive use of genetically engineered mouse models to study

human cancer genetics by integrating the study of mouse and human molecular genetics and by

cataloging mouse single nucleotide polymorphisms to facilitate genotyping of commonly used

mouse strains. $2.50

5. Support collaborative studies of high-risk individuals to address the clinical, behavioral,

and societal issues associated with cancer susceptibility .

■ Sustain the Cancer Genetics Network (CGN) as a resource for studies of clinical care for early

detection, diagnosis, and treatment of genetically high-risk individuals, including those from

minority and underserved populations. $10.00 M

■ Expand support for studies in cancer genetics that examine psychosocial responses to cancer risk

communication within average and high-risk populations in order to inform the development of

effective educational strategies and resources for patients, providers, and the public. $4.00 M

■ Continue to support research in cancer survivorship to evaluate physiologic and/or psychosocial

effects of cancer or its treatment among survivors of cancer, and examine the role of genetic factors in these sequelae. $2.00 M 

■ Refine cancer risk prediction method s / m odels to integrate genetic and environmental determinants of cancer by developing methods to estimate individual risk. Merge models that are primarily genetic based with those that are primarily environmental. Refine models that predict

cancer risk and other outcomes among diverse populations to estimate population burden and

policy implications. $1.00 M

■ Collaborate with the Centers for Disease Control and Prevention Genomics and Public Health

Centers to develop methodological standards specific to the collection and reporting of data from

NCI consortia on gene-environment interactions, effectively relating these results to medical

practice and public health. $0.50M

Management and Support

To t a l

$5.0 M

$17.5 M

$3.0 M

$55.5 M
64 The Nation’s Investment in Cancer Research

C o h o r t C o n s o r t i u m of investigators are involved

in a collaboration to uncover gene-environment

interactions by compiling and examining more

than 7,000 cases each of breast and prostate cancer. 

■ Two other groups of investigators are using the

case-control approach to identify genetic and

environmental determinants of non-Hod g k i n ’s

lymphoma (NHL) and brain cancer. These C a s e -

Control Consortia of investigators are pooling

data from more than 5,000 patients with NHL

and more than 3,000 with brain tumors. 

■ Two groups of researchers are partnering to collect

high quality cancer registry data on environmental exposures of patients and a variety of biologic

specimens from these patients for use in genetic

analysis. These data and analyses will be compared with those of non-cancer patients, and the

resulting information will serve as a resource for

the research community in its search for susceptibility genes and environmental carcinogens. 

Second, NCI is examining a broad spectrum of

approaches to assess and measure environmental

e x p o s u r e s .

■ Non-invasive methods for detecting cancers, carcinogenic exposures, and genetic susceptibility

can ease the stress on patients and make screening

for environmental exposures and early signs of cancer more thorough and affordable. These method s

also are well suited to use in large-scale research

studies. Researchers are examining options that

would allow doctors to detect cancer, carcinogenic

exposures, or genetic susceptibility by screening for

lung cancer using a molecular marker in sputum

samples; sampling DNA from cheek cells; using

saliva samples instead of blood to test for bod y

nutrient levels, hormones, and environmental

chemicals; or using urine samples to validate

patient responses to questions about dietary habits. 

■ New and easier methods, such as biod o s i m e t r y

and direct versus surrogate measures, may provide

improved ways of assessing difficult-to-measure

environmental exposures. 

■ Collaborative studies with the National Institute

for Occupational Safety and Health are i m p r o v -

ing assessment measures for studying cancer

resulting from exposure to low-dose radiation and

agricultural pesticides. Sophisticated monitors

designed for workers in specific occupations can

be used in large groups of workers. 

■ Techniques using geographic information systems to support the Long Island Breast Cancer

Study of complex toxicological and environmental exposures and breast cancer incidence can be

applied to other areas of research as well.

Third, we are advancing research to discover and

characterize cancer predisposing genes by building

on NCI-supported cancer family registries and promoting collaborations among investigators who have

studied large numbers of families with cancer.

■ The Cancer Family Registry (CFR) , a large international registry of more than 8,500 ethnically

diverse families and 21,000 participants, focuses on

highly penetrant breast and ovarian cancer genes

by recording information on cancer family history,

demographics, environmental and lifestyle risk factors, and clinical data and by maintaining a bank

of biological specimens. The CFR is supporting

several studies to provide the information needed

to make prevention and treatment decisions. One

such study examines the effects of hormones as

well as diet, body size, physical activity, alcohol

consumption, and radiation on breast cancer risk

among carriers of BRCA1 and BRCA2 mutations.

■ A second large resource, the Colon Cancer

Family Registry , has assembled data on more

than 5,000 families, including more than 150 families with hereditary non-polyposis colon cancer

and more than 300 with two or more first-degree

relatives who have the cancer.

■ Other groups of investigators are working to discover and characterize highly penetrant familial

genes associated with melanoma, ataxia telangiectasia, and prostate and lung cancers.

Fourth, NCI is supporting the development of a

number of tools for use in gene discovery and chara c t e r i z a t i o n . These efforts are needed to advance our

understanding of gene-environment interactions and

the application of that knowledge.

■ Through the Mouse Models of Human Cancers

Consortium (MMHCC) , scientists are capitalizing on the remarkable correspondence between

the human and mouse genomes to identify human

c a n c e r-related genes and are facilitating rapid cancer gene discovery by adding mouse models of

known familial cancer susceptibility genes. In collaboration with population scientists studying

cancer families, MMHCC researchers applied a

64 The Nation’s Investment in Cancer Research
new timesaving strategy of mouse cross-breeding

to quickly pinpoint the BRCA1 breast cancer susceptibility gene. The mouse studies soon revealed

the function of the gene and enabled scientists to

verify its role in altering susceptibility to breast

c a n c e r. Furthermore, a model for the gene

PTEN/MMAC1 may shed light on several types of

c a n c e r, including Cowden disease, a syndrome

that predisposes family members to breast, brain,

prostate, endometrial, and bladder cancers. 

■ NCI used a risk assessment model that combines

several known risk factors in the Tamoxifen Breast

Cancer Prevention Trial. The success of the mod e l

exemplifies how we can substantially increase our

ability to predict breast cancer risk. Scientists have

greatly expanded information on risk factors

among African American women and are incorporating data from the Wo m e n ’s Health Initiative

Trial. Using this Gail Model as a pattern,

researchers are now constructing models for both

ovarian cancer and colorectal malignancies built

on pooled data from large multi-center studies. 

■ Through the efforts of the Genetic Annotation

Initiative (GAI), the genetic information generated by the Cancer Genome Anatomy Project

(CGAP) is being made available for research use.

More than 30,000 gene-based polymorphisms –

DNA variations among individuals – have been

identified, and GAI scientists have established

high-throughput laboratory assays to detect more

than 7,000 of these variants. As with all of the

CGAP resources, materials are available free of

charge through the World Wide We b

(cgap.nci.nih.gov). Scientists can use these tools

to investigate the roles of these genes in families

and populations.

Fifth, NCI has established a productive infrastructure to support intervention trials on inherited susceptibility to cancer. Such trials are vitally important

to improving our ability to detect and treat cancer

e a r l i e r. Through the Cancer Genetics Network

( C G N ), researchers are conducting a number of these

studies. (1) A pilot study of an early detection technique for ovarian cancer screening in genetically susceptible women involves a CGN partnership with

several NCI-supported programs, including the

Gynecologic Oncology Clinical Trials Group. (2) In

another study, researchers are comparing the effectiveness of several existing biostatistical models for

estimating breast cancer risks. (3) Another group is

developing innovative analytical methods to identify

colon cancer genes that are as yet undiscovered. (4)

A pilot study will improve methods for recruiting and

retraining individuals and families at high risk of cancer into clinical trials. (5) Finally, a pilot collaborative is coordinating a multi-institutional study of

genetic and environmental modifiers of cancer risk in

women with BRCA1 and BRCA2 mutations.

To apply the latest findings in human epidemiologic and clinical investigations, the CGN is promoting active collaboration with the Mouse Models of

Human Cancers Consortium, the Genetic

Annotation Index, and the Cancer Genome

Anatomy Project. In addition, CGN is collaborating

with the NCI Special Populations Networks for

Cancer Awareness Research and Training to ensure

wider opportunities for people from diverse communities, including investigators representing those

communities, to participate in research on genetic

susceptibility to cancer.

Extraordinary Opportunities 65

E n v i r onmental Exposures and Inherited

Susceptibility in Cancer

S c ie nt i f ic stud ies point to three main catego r ies of enviro n me ntal ex p o s u res that contribute to the de v e l o p me nt

of canc e r.

C h e m i c a l s

■ C he m icals in the die t

■ Ho me or workplace ex p o s u re s

■ D r u g s

■ Po l l u t a nts in the air, water, or soil

R a d i a t i o n

■ Low stre ngth ra d ia t ion such as ultra v iolet ra d ia t io n

f rom sunlig ht

■ H igh stre ngth ra d ia t ion as from x-rays or 

ra d io i s o t o p e s

Viruses and bacteria

■ Epstein-Barr virus — Burkitt’s lympho ma

■ Hu man papillomavirus — cervical canc e r

■ Hepatitis B virus — liver canc e r

■ Hu man T-cell lympho t ro p ic virus — adult T- c e l l

l e u ke m ia

■ Kaposi’s sarc o ma associated herpes virus — Ka p o s i ’ s

s a rc o ma

■ H. pylori bacteria — associated with stomach canc e r

A person’s chances of de v e l o p i ng cancer can also be 

i n f l u e nced by the inhe r i t a nce of certain kinds of ge ne t ic

a l t e ra t io ns. Specific inherited mu t a t io ns inc rease a 

person’s risk of de v e l o p i ng some cancers inc l ud i ng

b reast, colon, kid ne y, bone, and skin. As we better

u nde r s t a nd the interplay between inherited susceptibility to cancer and enviro n me ntal risk fa c t o r s, we can

develop mo re me a n i ngful appro a c hes to cancer care.
66 The Nation’s Investment in Cancer Research

2

E x t ra o r dinary Opportunities for Inv e s t m e n t

Cancer Imaging

THE OPPORTUNITY

A

s recently as 25 years ago, a physician or surgeon

who suspected the presence of a tumor in a patient

had few options. The normal course of events would

be to order x-ray studies to find the tumor’s exact location, schedule the patient for surgery, excise a portion

of the unhealthy tissue for biopsy, remove the tumor,

and explore surrounding tissues to determine if the

cancer had spread. But over the last quarter century,

improvements in imaging technology have substantially broadened the range of medical options. Wi t h

the power of imaging technology now available,

physicians can get much clearer and more detailed

pictures of organs and tissues, and they

can view far more than anatomical

structures such as bones, organs, and

tumors. Using “functional imaging” for

the visualization of physiological, cellul a r, or molecular processes in living tissue, physicians can examine activities

such as blood flow, oxygen consumption, or glucose metabolism as they take

place. 

M odern imaging technology already

h as had lifesaving effects on our ability to detect cancer early and more accurately diagnose the disease. 

X-ray mammography, for example, has revealed the

presence of very small cancers in thousands of women

before the tumors could be detected by physical examination. And computed tomography (CT) can show if

a tumor has invaded vital tissue, grown around blood

vessels, or spread to distant organs. As the science continues to advance, we will be able to detect changes in

the workings of a cell as it becomes malignant and use

this information to diagnose cancer earlier. 

E v e n t u a l l y, we may be able to detect changes in

the activity and function of specific genes in a

p a t i e n t ’s cancer cells, and use that information to

choose the best treatment option. In addition to

using CT and other imaging technologies to guide

treatment choices, scientists have developed method s

for combining imaging techniques with radiation

sources and high-performance computing. This

serves to better target radiation treatments to a

t u m o r ’s three-dimensional contours, thus minimizing

damage to surrounding, healthy tissue. Moreover,

with tod a y ’s technology, we can also identify the

molecular characteristics of a tumor and use that

information to predict how it will respond to certain

treatments. With a visual image of how glucose is

being used in cancer cells, we can tell – without the

need for a biopsy – how a tumor is responding to a

recently administered treatment.

Oncologists also increasingly rely on image-guided

t h e r a p y, in which imaging is combined with various

t u m o r-killing approaches (toxic chemicals, gene thera p y, heat, and cold). By allowing physicians to better distinguish between cancerous and normal tissue and target

treatments to diseased tissues, imageguided therapy can minimize surgical

trauma, shorten recovery time, improve

patients quality of life, and reduce

health care costs. 

N C I ’s opportunity is to further

improve cancer imaging technologies

with the goal of ensuring earlier and

more accurate diagnoses for more cancer patients,

reducing the number of invasive therapies needed to

treat their illnesses, and improving physicians’ abilities to monitor patient responses to treatment. Wi t h

investments in research and development, significant

advances in cancer imaging are now possible and will

ultimately save more lives. 

PROGRESS IN PURSUIT OF OUR GO A L

A

dvances in cancer imaging research and technology over the last 25 years have demonstrated

their potential to profoundly affect the practice of

oncology and extend patients’ lives, and NCI’s continued investment is yielding further tangible

progress in developing better imaging technologies

for both cancer research and clinical practice. 

66 The Nation’s Investment in Cancer Research

G O A L

Accelerate disco very and

development of imaging

methods that will predict

clinical course and

response to 

interventions .
Developing Better Imaging Technologies

and Techniques

NCI has played a major role in fostering molecular or

f u n c t i o n a l1imaging. Through initiatives such as I n

vivo Cellular and Molecular Imaging Centers

( I C M I C s ) , NCI has nurtured and promoted molecular imaging by supporting essential infrastructure and

providing career stability to investigators in this

emerging field of research. Each Center brings together experts such as biomedical engineers, cellular and

molecular biologists, pharmacologists, and imaging

scientists to conduct a program of multidisciplinary

research on cellular and molecular imaging in cancer. 

One of the ICMICs has led the way in developing

“smart contrast agents.” When smart contrast agents

are injected into the bod y, they are undetectable.

H o w e v e r, when they come into contact with tumorassociated enzymes called proteases, the smart agents

change shape and become fluorescent. The fluorescent signal can then be detected using sophisticated

imaging devices. This first generation of smart agents

are being further refined and developed by ICMIC

investigators and will have important applications in

tumor detection and therapy assessment in the future.

At the start of 2000, NCI established ICMICs at

three sites around the country. The Institute has also

awarded planning grants to 16 universities and

research centers to begin to bring together investigators from a range of fields and initiate research projects in molecular imaging. NCI will select two of

these to become full-fledged Centers by the end of

2001. In addition to their research activities, ICMICs

will train new investigators and provide established

investigators an opportunity to develop a multidisciplinary understanding of imaging, the basic science of

c a n c e r, and cancer care. 

NCI is also helping to foster the development of

new imaging contrast agents and molecular probes to

improve the diagnosis and treatment of cancer

through the Development of Clinical Imaging Drugs

and Enhancers (DCIDE) program. In the first year

of DCIDE, two agents were selected for further development: (1) a new contrast agent that enhances

positron emission tomography (PET) imaging by targeting elevated levels of an enzyme present in

prostate and other cancers and (2) a probe that can

improve the accuracy with which magnetic resonance imaging (MRI) can reveal the earliest stages of

the new blood vessel growth that accompanies a

developing tumor. 

Animal models of cancers play an invaluable role

in research, enabling scientists to investigate the

development and progression of cancer; test new

approaches to detection, diagnosis, and imaging; and

evaluate prevention and treatment. With improved,

genetically engineered mouse models for cancer

becoming more widely available, investigators are

able to use laboratory mice to study the development

and spread of cancer and to test improvements in cancer imaging through the use of specialized equipment

and techniques for imaging small animals. Since

1999, NCI has funded Small Animal Imaging

Resource Programs at five research centers around

the country to make the necessary equipment and

personnel available to investigators and to improve

and enhance technologies and techniques for imaging small animals. 

Investigators working with the Small Animal

Imaging Resource Program at one university, for

example, have been exploring the use of diffusion

MRI, which measures the movement of water through

and between cells for imaging brain tumors. After validating their approach in small animals, imaging specialists have begun to test this new form of MRI in

patients with brain tumors and other cancers. Initial

results in patients, especially children, look very promising. If proven effective, diffusion MRI could dramatically reduce the time required to determine

whether cancer patients are responding to therapy.

Given the success of the Small Animal Imaging

Resource Programs to date, NCI funded five additional programs in 2001. In addition, the Institute is

actively working to foster broader use of these technologies. For example, NCI will co-sponsor a conference on the techniques of small animal imaging in

September 2001, and has awarded supplemental

funding to a number of scientists involved in the

Mouse Models of Human Cancers Consortium to

incorporate imaging research into their work. 

NCI, with the National Science Foundation, i s

cultivating further advances in the development of

noninvasive imaging, monitoring, and therapeutic

systems, with two projects focusing on the development of miniaturized optical probes. These probes,

Extraordinary Opportunities 67

1 Molecular imaging techniques do not actually reveal molecules themselves, but detect signals that indicate the presence of biochemical activity and changes, such as cell growth or

death. Thus, molecular imaging is often described as “functional”, because the processes being imaged are active and constantly changing.
68 The Nation’s Investment in Cancer Research

THE PLAN — CANCER IMAGING 

Goal

Accelerate discovery, development, validation, and clinical feasibility of imaging methods to

identify the biological and molecular properties of precancerous or cancerous cells that will 

predict clinical course and response to interventions.

Objectives and Milestones for Fiscal Year 2003

1. Expand the discovery, design, and development of novel imaging agents and devices.

■ Establish two additional In Vi v o Cellular and Molecular Imaging Centers (ICMICs) to foster

multidisciplinary research on cellular and molecular imaging in cancer. $4.00 M

■ Establish a Network for Optical Technologies Development. $4.00 M

■ Increase the number of imaging agents supported by the Development of Clinical Imaging

Drugs and Enhancers Program from 6 to 10 per year. $4.00 M

■ Use research supplements to increase collaborations between Small Animal Imaging Resource

Programs (SAIRPs) and other NCI programs such as the Mouse Models of Human Cancers

Consortium. $2.00 M

■ Speed the development of specific imaging agents by funding grantees in a variety of NCI programs, such as ICMICs, SAIRPs, Interdisciplinary Research Teams for Molecular Ta r g e t

Assessment, Molecular Target Drug Discovery, and Molecular Target Laboratories. $2.00 M

■ In collaboration with the developers, provide to academic institutions for feasibility testing,

innovative imaging device prototypes, selected through a new competitive program, that have

a limited market or face other barriers to commercialization. $5.00 M

■ Support and add information to a publicly available database of imaging agents for the research

c o m m u n i t y. $0.10 M

■ Establish data banks of standardized digital image data (such as virtual colonoscopy, digital

m a m m o g r a p h y, digital chest imaging, and optical imaging for applications such as cervical,

prostate, and oral cancers) associated with known clinical outcomes to provide research

resources for a variety of investigators. $2.00 M

■ Fund six to eight grants to develop and test image processing and analysis algorithms (artificial

intelligence) using these standardized data sets. $2.00 M

$25.1 M

which provide very high-resolution images, are capable of detecting changes at the molecular level. 

Bringing A d vances in Imaging to 

Cancer Care 

As new cancer imaging technologies and techniques

emerge and are refined, they often undergo further

evaluation through one of NCI’s clinical trials cooperative groups. These are networks of health care professionals affiliated with medical schools, teaching

hospitals, and community-based cancer treatment

centers. For example, NCI’s newest cooperative

group, the American College of Radiology Imaging

Network (ACRIN) , is assessing the value of computed tomography (CT) scanning in screening patients

for colon cancer, a technique sometimes known as

“virtual colonoscopy.” Because patient cooperation is

critical to the success of any type of cancer screening,

another group of NCI-funded investigators is also

looking at patient preferences as one component of

their comparisons of virtual colonoscopy and more

traditional methods of colon cancer screening. 
Extraordinary Opportunities 69

2. Integrate molecular and functional imaging methods into therapeutic clinical trials.

■ Increase the contract support for early clinical trials of imaging agents (safety and efficacy 

studies) from 8 to 12 trials per year. $2.00 M

■ Provide expertise to clinical trials that use imaging by funding supplements or grants for 10 to

15 imaging cores within NCI-funded Cancer Centers. $4.00 M

■ Support expert panels to develop consensus criteria for using imaging results as endpoints in

clinical trials. $0.20 M

3. Increase clinical trials of imaging methods and technologies.

■ Expand a large randomized clinical study of spiral computed tomography as a screen in the

detection of lung cancer, if initial data show a larger study is needed. $20.00 M

■ Initiate clinical studies to: compare CT colonography (virtual colonoscopy) with endoscopic

colonoscopy for early detection of colon cancer and polyps in a large multi-institutional setting; evaluate magnetic resonance spectroscopy for the early detection and assessment of

prostate cancer; and evaluate the role of FDG-PET studies for monitoring tumor response to

t h e r a p y. $4.00 M

■ Support corollary imaging studies, such as monitoring response to therapy, with 10 funding supplements to Clinical Trials Cooperative Groups. $4.00 M

■ Support the development of the tools and infrastructure for the use of functional and molecular

imaging in conjunction with radiation therapy, using novel treatment approaches including

intensity modulated radiation therapy. $2.00 M

4. Accelerate the development and clinical testing of image-guided interventions.

■ Use 6 to 10 funding supplements to enhance programs such as the SPOREs for image-guided

therapy research that emphasizes a problem-solving, organ-specific approach and promotes

interactions between clinicians and bioengineers. $3.00 M

■ Increase collaborations between the other Clinical Trials Cooperative Groups and the

American College of Radiology Imaging Network (ACRIN) for testing promising, minimally

invasive, image-guided interventions with four to six funding supplements. $2.00 M

Management and Support

To t a l

$6.2 M

$30.0 M

$5.0 M

$3.5 M

$69.8 M

ACRIN investigators are also evaluating the use of

C T, MRI, and traditional tests for determining the

spread of cervical cancer. To definitively answer questions about the value of digital mammography for

breast cancer screening, ACRIN investigators have

launched the largest study ever to compare conventional and digital mammography. They plan to compare the two methods in nearly 50,000 women over

the next few years. 

At the same time, other NCI-sponsored networks

are also evaluating the use of imaging technologies.

Another cooperative group, the American College of

Surgeons Oncology Group , is actively studying the

use of PET scanning in patients with lung and

esophageal cancer, to determine how far the disease

has advanced. In addition, investigators involved in

the Lung Cancer Screening Study are comparing the

use of spiral CT with traditional chest x-rays in screening for lung cancer. A number of other investigators 
70 The Nation’s Investment in Cancer Research

around the country are working to improve diagnostic

imaging and image-guided therapy for prostate cancer. 

In addition to evaluating the use of various imaging

technologies and screening and treatment procedures,

NCI-supported scientists are using sophisticated i m a ging to assess the effects of new cancer drugs. For example, with many drugs that prevent the growth of new

b l o od vessels, tumor shrinkage may not be readily

apparent for some time. In cases such as these, functional imaging techniques can reveal whether the

tumor is responding to therapy. 

The integration of new imaging technologies in

radiation oncology will not only improve the targeting of a tumor but will allow for the delivery of a more

exacting radiation dose to areas within the tumor

defined by functional imaging. This targeting has the

potential to not only improve tumor control but also

minimize toxicity. This complex technology requires

enhanced treatment planning, quality assurance, and

data transfer. NCI is supporting a consortium to

develop the necessary tools through the A d v a n c e d

Technology Radiation Therapy Clinical Trials p r ogram. 

Biomedical opportunities and scientific advances

drive technology development in cancer imaging, but

NCI recognizes that the regulatory environment in

which this development takes place is critically

important. To facilitate the transition of emerging

cancer imaging technologies into medical practice,

NCI created and coordinates a “sounding board” of

Federal agency staff that advises investigators and

manufacturers seeking to bring new imaging technologies to the marketplace. This group, the

Interagency Council on Biomedical Imaging in

O n c o l o g y , consists of staff from NCI, the Food and

Drug Administration (FDA), and the Centers for

Medicare and Medicaid Services (formerly the Health

Care Financing Administration). Council members

provide advice to technology developers from academia and industry and discuss the evaluation of emerging technologies. Since September 1999, NCI has

also co-sponsored with industry an annual national

conference on biomedical imaging in oncology that

focuses on the research, regulatory, and reimbursement pathways of technology d e v e l o p m e n t .

Highlights of Recent Advances in

Cancer Imaging

High-Powered Microscope T racks Cell Changes .

With funding from NCI, a multidisciplinary team

of physicists, biologists, optical experts, and

chemists has developed a new type of microscope combining the capabilities of nuclear 

magnetic resonance imaging with those of a 

traditional microscope. Using the combined

microscope, investigators can examine how living

cells react to changes in their environment, track

the development of cancer, and study how cancer

cells respond to treatment. In light of its 

potential significance for biomedical research,

Discover Magazine recognized the new microscope

and the leader of the research team that 

developed it with its 2001 Award for

Technological Innovation in Health. 

New Imaging Tools Pr ovide More Accurate and

Complete Diagnosis .

Two groups of NCI-supported investigators 

working to improve cancer screening recently

received Food and Drug Administration approval

for computer-aided diagnosis systems to help

radiologists assess the results of mammograms

and chest x-rays. In these systems, computers

are programmed to identify and highlight

suspicious “hot spots” to ensure that all 

potentially cancerous points are examined.

Optical Biopsies an Option for the Futur e.

NCI-funded scientists are developing imaging

systems that may permit patients to undergo

“optical biopsies” in the future and allow 

physicians to diagnose cancer without the need

for tissue samples. By mo d i f y i ng endoscopes and

similar ins t r u me nts to pro v ide very hig h - re s o l u t io n

images for examining the gastrointestinal 

system, lungs, and other internal organs,

investigators can now identify the cellular

changes typical of early cancer when it is most

treatable. In cases where these more powerful

images can rule out cancer, such optical biopsies

will allow patients to avoid unnecessary and

painful tissue biopsies.
THE OPPORTUNITY

O

ur bodies are made up of many different kinds of

cells, and each is suited to its particular function as

a part of the whole. Scientists are discovering that

every cell type has a unique molecular signature – identifiable characteristics such as levels or activities of a

myriad of genes, proteins or other molecular features.

Today researchers are using new technologies to read

and understand the signatures of normal cells and how

they can change to become cancerous. They are learning to identify signature changes in developing tumors,

in surrounding cells, and sometimes at more distal,

more easily sampled sites of the body – such as sampling cells in the mouth instead of the

lung or sampling urine to detect urinary

tract cancer. Molecular signatures can

also be used to identify cancer- c a u s i n g

infectious and environmental agents. 

The extraordinary opportunity of

molecular signatures is expected to help

the cancer community learn how to diagnose cancer early before it has a chance

to do harm, to compose highly effective

treatments tailored to the features of each

case, and to monitor the patients recovery.

To succeed in this effort we will need a full understanding of how cancer starts and progresses, especially

focusing on how small changes in only a few genes or

proteins can disrupt a variety of cellular functions. This

work will require new technologies, new pre-clinical

m odels and heightened cooperation between investigators from all disciplines of cancer research. Our ultimate

objective is to push back the detection and diagnosis of

cancer to the earliest stages when prevention of overt

disease can be most successful. 

PROGRESS IN PURSUIT OF OUR GOAL

T

he NCI is providing resources needed to study the

molecular signatures of cancer including catalogs

of molecular changes in cancer at the chromosomal

and gene levels, genes, tissues, and other biologics for

s t u d y, new technologies, and informatics tools.

Molecular and Analytic Resources to

Stimulate Research 

NCI is creating molecular and analytic resources

through genetic profiling and technology development. The Cancer Genome Anatomy Project

( C G A P ) (cgap.nci.nih.gov) is a multiinitiative NCI program to build a complete profile of

genes expressed in normal, precancerous, and cancer

cells. This resource is helping investigators to elucidate major steps of tumor development, develop

molecular diagnostic techniques, and identify molecules that can be used for early detection

or drug discovery. Researchers throughout the world have used CGAP to identify molecular signatures of prostate,

colon, ovary, breast, pancreas, brain, and

other cancers. 

One CGAP initiative, the Tu m o r

Gene Index (TGI) , containing more

than five million gene-based DNA

sequences, is the most complete public

catalog of gene expression for human cancers and for mouse models of cancer. Scientists already

are using TGI to classify tumors according to their

molecular features for improved cancer prevention,

early detection, diagnosis, and treatment strategies.

Through TGI we hope to build a complete index of

c a n c e r-related genes.

CG A P ’s Mammalian Gene Collection (MGC) i s

extending the TGI to focus on identifying and cloning

the full set of human and mouse genes to enable more

rigorous study of individual genes, their protein products, and the role they play in human disease.

C u r r e n t l y, potentially full gene sequences have been

identified for about 15,000 human genes and 8,000

mouse genes. 

T h e CGAP Genetic Annotation Initiative (GAI)

has characterized and cataloged more than 30,000

human genetic polymorphisms. Polymorphisms are

variations, sometimes quite subtle, in the DNA

Extraordinary Opportunities 71

3

E x t ra o r dinary Opportunities for Inv e s t m e n t

Defining the Signatures of Cancer Cells: 

Detection, Diagnosis, and Ther a py

G O A L

Catalog distinguishing

molecular signatures o f

cells to de velop ne w

diagnostic and therapeu -

tic approaches and pr edict response .
72 The Nation’s Investment in Cancer Research

THE PLAN — DEFINING THE SIGNATURES OF CANCER CELLS:

DETECTION, DIAGNOSIS, AND THERAPY

Goal 

Generate a complete catalog of the distinguishing molecular signatures of normal, precancerous,

and cancer cells at all stages in all tissues, and use the catalog to develop diagnostic techniques

for the earliest detection of precancerous lesions and cancers; develop signature-based therapies;

and identify subsets of patients with different prognoses to predict therapeutic response. 

Objectives and Milestones for Fiscal Year 2003 

1. Expand the development and availability of molecular and analytic resources. 

■ Initiate the Cancer Molecular Analysis Project to integrate molecular signatures, targets, and

interventions. $5.00 M

■ Complete the Mammalian Gene Collection for full-length human and mouse cDNAs. $3.00 M

■ Continue to develop technologies relevant to discovering and measuring molecular signatures

of cancer and precancer and the dissemination of technologies to the scientific community

$1.00 M

■ Continue to develop biosensors for detecting human cancer and cancer development through

the Unconventional Innovation Program. $6.50 M

■ Extend the Genetic Annotation Initiative to identify new cancer related gene polymorphisms

in defined populations, define key molecular pathways by thoroughly characterizing genetic

variations on numerous gene and protein expression profiles, and develop human gene expression profiles from specific tissues with measured exposure times to study epigenetic4

targets and

cell pathways that lead to tumor formation. $3.00 M

2. Establish and make available to researchers tissue resources to maximize the practical

application of molecular signatures to problems in cancer research.

■ Establish a national tissue resource system for all major cancers, including lung, breast, prostate,

colon, head and neck, brain, soft tissue, blood, bone, the gynecologic and genitourinary, and

c h i l d h o od malignancies. $4.00 M

■ Expand tissue repositories of precancerous lesions in all major cancers. $4.00 M

■ Use Phased Innovation Awards to develop tissue preservation and sample preparation method s

to increase their utility and compatibility with new research technologies. $4.00 M

■ Enhance the Web-based system to query pathology information systems, including pathology

standardization and agreement on common data elements. $2.50 M

3. Identify molecular signatures and apply them to the study and validation of animal 

models for human cancer .

■ Continue to develop preclinical mouse models and fund systematic analysis and phenotyping

to validate them. Use these models to validate new molecular-based approaches for early

detection, diagnosis, treatment, and prognosis of human cancer. $5.00 M

$18.5 M

$14.5 M

$5.0 M
Extraordinary Opportunities 73

4. Support new approaches for early detection of cancer and to determine biomarkers of

precancerous lesions.

■ Identify easy-to-sample sites remote from the tumor itself, for more cost-effective, earlier cancer

detection and risk assessment. $2.00 M

■ Study molecular signatures to discover the causes of cancer, including infectious and environmental agents. $1.00 M

■ Identify and validate biomarkers to develop effective, reliable tools for early cancer detection

and to assess their potential for predicting cancer. $2.00 M

■ Develop a program that uses the patterns of very small proteins in serum for early diagnosis of

prostate, breast and ovarian cancer. Expand marker identification to predict disease stage and

risk of recurrence. $2.00 M

■ Expand studies to identify and validate epigenetic markers of cancer. $1.00 M

■ Develop applied algorithms and statistical methods to analyze multiple biomarkers and patterns

of molecular changes and link those changes with clinical outcomes. $1.00 M

■ Develop analytical prediction tools for risk assessment, incorporating molecular, genetic, and

family history information. $1.00 M

■ Implement within the Early Detection Research Network, a Network-Wide Knowledge and

Informatics Center. $1.00 M

5. Validate molecular classification schemes of cancer, and develop new diagnostic tests.

■ Expand validation programs for each major cancer site as results emerge from the Director’s

Challenge and other programs. 

■ Validate new diagnostic approaches through the Program for Assessment of Clinical Cancer

Tests to provide the research community with a means to evaluate and validate signatures with

possible diagnostic value. 

6. Support basic research aimed at characterizing aberrant molecular interactions in cancer .

■ Generate a comprehensive map of all cellular signal transduction pathways1 and their links to

one another through a Signal Transduction Annotation Consortium. $5.00 M

■ Support basic research efforts for analysis of: important cell structure that may be disrupted in

cancer; organization and location of chromosomes during cell reproduction; structure and function of molecular machines; and structure and function of membranes. $2.00 M

■ Develop technologies for analyzing cell-cell interactions and communication that might be 

disrupted in cancer by funding 10 Phased Innovation Awards. $2.00 M

Management and Support

To t a l

$11.0 M

$13.0 M

$9.0 M

$4.0 M

$75.0 M

1 Molecular pathways that translate a signal from outside the cell to a functional change in the cell.
74 The Nation’s Investment in Cancer Research

sequences of a gene that may affect its function. The

GAI provides scientists with insights about genetic

variants associated with certain cancers and those

that occur more frequently in some populations. 

The Cancer Chromosome Aberration Project

(CCAP) was established by CGAP to generate 

a “Human Cancer Chromosome Aberration Map” –

a genetic map that defines distinct chromosomal

alterations that lead to cancer. Investigators are using

a molecular tool known as BAC (bacterial artificial

chromosomes) clones. BAC clones are derived from

bacteria and contain florescent probes as well as

inserts of human DNA sequences. The human DNA

inserts are designed to bind to aberrant sections of

DNA in the samples being tested in the laboratory.

Researchers are able to confirm the presence of an

aberration by measuring florescence in the sample. In

2001, CCAP passed a major milestone by prod u c i n g

an online version of the Mitelman Database of

Chromosomal Aberrations in Cancer, a well-established and exhaustive reference of chromosome

changes in human tumors. In 2002, CCAP will complete a map that integrates structural mapping of the

human genome with chromosomal maps. (See page 53

for more information on CGAP.) 

The Innovative Molecular Analysis T e c h n o l o g i e s

Program (IMAT ) supports the development of technology to detect molecular signatures in small numbers of cells. This technology is needed to detect cancer at its earliest stage and to study its origins. More

than 100 research projects are under way, focusing on

new approaches to analyze DNA, RNA, and proteins, as well as new methods to detect interactions of

macromolecules in the cell. 

Through the Unconventional Innovations

Program, NCI is supporting creative technological

improvements in cancer treatment and detection in

the 21st century. This program aims to generate radically new technologies in cancer care to make

attainable the goal of detecting, diagnosing, and

intervening in cancer at its earliest stages. It targets

improvements in existing technologies or new

approaches and actively stimulates the interest and

involvement of investigators from disciplines not traditionally focused on NCI’s technology challenges. 

Tissue Resources for Signatures Research

Clinical specimens are a critical resource for the discovery and application of molecular signatures to

cancer detection, diagnosis, and treatment. NCI has

established and made readily available to researchers

a variety of tissue repositories.

T h e Cooperative Human Tissue Network

(CHTN), Cooperative Breast Cancer T i s s u e

Resource, and Cooperative Prostate Cancer T i s s u e

Resource all provide researchers with easy access to

high-quality tissue specimens. For example, the

CHTN alone is now providing close to 50,000 

samples per year. More than 1,000 investigators have

been served by the CHTN, and about 200 new investigators request tissue each year.

The Shared Pathology Informatics Network , a

consortium of institutions connected by a model We b -

based system, is working to improve scientists’ access to

human specimens and relevant clinical data. The system will automatically access information from medical databases and respond to queries by identifying,

obtaining, and returning data for specimens that

meet the defined search criteria, after removing 

information that could compromise patient privacy. 

The Tissue Array Research Program (T A R P )

( c a n c e r.gov/tarp) stemmed from collaboration among

scientists at NCI and the National Human Genome

Research Institute and is responsible for the development of multi-tumor, tissue screening m i c r o a r r a y

slides. The slides contain up to 600 tissue core samples from different tumor tissues as well as normal

tissue and specific cell lines grown in the laboratory.

Researchers use the slides for high-throughput, c o mprehensive analysis of the molecular profile of each

tumor type represented on the slide, including characterization of DNA, RNA, and proteins. The slides

also can be used to further characterize molecules as

potential molecular targets unique to each tumor tissue (see page 78). As of 2002, approximately 11,000

array slides were distributed to researchers nationwide. TARP plans to scale up production of these

slides and is establishing a knowledge transfer and

training program to disseminate this technology to

interested scientific investigators.

Using Molecular Signatures to Study and

Validate Animal Models of Human Cancer 

M odels that accurately reflect the behavior of human

cancer promise to improve our ability to identify and

understand the molecular changes that characterize

cancer as well as enhance our ability to evaluate a

range of biomarkers prior to clinical use. NCI

launched the Mouse Models of Human Cancers

C o n s o r t i u m to develop and make available to

researchers validated mouse models that mimic human

cancers. See page 58. 

74 The Nation’s Investment in Cancer Research
Molecular Signatures and New Approaches

for Early Detection

NCI established the Early Detection Research

Network (EDRN) in 1999 as a research program

aimed at the discovery and development of novel biomarkers for all cancers and for precancerous lesions.

Separate EDRN laboratories cooperate to streamline

the development, validation, and clinical testing of

promising biomarkers and technologies for cancer

screening and detection. This comprehensive, collaborative approach merges genetic pursuits with protein

approaches, providing a systematic view of how the

molecular signatures of specific cancers can be used as

unique, identifying markers. 

EDRN researchers have discovered biomarkers for

the early detection of several types of cancer, including breast, esophageal, and prostate. In breast cancer

studies, researchers are hoping to develop a noninvasive detection test for breast cancer based on proteins

present in nipple aspirate fluid (NAF). NAF circulates in the breast ducts and contains proteins produced by the breast. An easily extractable fluid, NAF

may provide a “snapshot” of the breast environment.

Investigators have identified differences in proteins in

NAF samples from a cancerous breast compared with

a normal breast in the same patient and are now testing the validity of this approach with a large number

of specimens. Other studies are exploring new

approaches to detect esophageal cancer at its earliest

stages, when the disease is most amenable to intervention. Preliminary EDRN data suggest that gene

microarrays may be used to detect premalignant and

malignant esophageal lesions with a high degree of

a c c u r a c y. If validated, these expression profiles offer

the potential of classifying esophageal lesions by their

a g g r e s s i v e n e ss and by their responsiveness to chemoprevention. Other researchers are using protein

microarray technology to improve the sensitivity

and specificity of tests for prostate cancer. Through

this research, they have observed that the serum

protein PSMA is superior to PSA, the marker currently used for prostate cancer screening, in distinguishing prostate cancer from benign growth. 

Better Classification of Tumors to

Improve Diagnostic Tests

Tumors have traditionally been classified according to

structural characteristics and not on molecular 

features that would better predict their biological

b e h a v i o r, treatment response, and prognosis. 

Through the D i r e c t o r ’ s Challenge: Toward a

Molecular Classification of T u m o r s initiative, investigators are developing profiles of molecular alterations

in human tumors using DNA, RNA, or protein-based

analysis technologies. These efforts will shift the focus

of tumor classification from structure to molecularbased schemes which may be used to define clinically

important subsets of tumors, helping health care

providers choose the best individual prevention and

treatment options. 

D i r e c t o r ’s Challenge teams are working on several

cancers including breast, prostate, lung, brain, ovary,

colon, and leukemia and lymphoma. One team is

working to subclassify node-negative breast cancer

patients. Node negative/positive is a traditional classification based on whether cancer can be detected in

local lymph nodes. While it is known that node positive patients have a considerable risk of cancer recurrence, this classification scheme cannot predict this

risk for node negative patients. This molecular subclassification appears to address this problem and

researchers are working to validate their findings for

use in a clinical setting.

The Program for the Assessment of Clinical

Cancer Te s t s ( PACCT) facilitates the translation of

new knowledge about cancer and new technologies

to clinical practice. Activities include the generation

of reference sets of clinical specimens, which will be

made available to academic and industry researchers

working to evaluate new markers and validate the

utility of some known markers and tests. 

Extraordinary Opportunities 75
M

ay 10, 2001, marked an important milestone

in the fight against cancer. News outlets all

over the country announced that a promising

drug called GleevecT M had been approved to treat a

serious blood cancer known as chronic myelogenous

leukemia (CML). The drug is one of the first of its

kind to be approved — a t a r g e t e d agent that hones in

on specific molecules in cancer cells, leaving healthy

cells unharmed. 

But the development of GleevecT M is far from an

overnight breakthrough. The road to its discovery

was paved through knowledge culled from more than

40 years of studies probing the molecular events associated with cancer development, the use of new technologies that enabled scientists to move in directions

previously beyond reach, and quite often, unanticipated opportunity. The story involves four key steps:

learning the unique chromosomal abnormalities of

CML, identifying the related cancer-causing protein,

finding a treatment agent that targets that protein,

and testing and proving its effectiveness and readiness for use in treating cancer. 

The Philadelphia Chromosome: Uncovering

the Fundamental Nature of CML

1960The story really began in 1960 whenDrs. Peter Nowell and David

Hungerford, two Philadelphia-based physicians, made

a curious discovery. They noticed that cells from

CML patients were missing a short segment on one

member of the 22nd pair of chromosomes. This shortened chromosome became known as the

“Philadelphia chromosome.” It was the first chromosome abnormality ever found to be associated with a

specific cancer and the first indication that tumors

might indeed arise from changes beginning in just one

cell. While the link between the Philadelphia chromosome and CML led scientists to suspect a causal

relationship, the location of the missing DNA from

chromosome 22 and how it might lead to CML was a

mystery to be solved over the next three decades. 

1970In the early 1970s, new staining techniques offered a way to more precisely

visualize band patterns, characteristic markings that

can be used to identify individual chromosomes. Wi t h

this technique, Dr. Janet Rowley determined that

chromosome 9 in CML patients was lengthened by the

same amount that chromosome 22 was shortened.

From this observation, Rowley proposed that the

genetic material from the two chromosomes was reciprocally exchanged, or “translocated.”

1980Using newly developed approaches formolecular analysis, scientists in the

early 1980s determined that the genetic rearrangement that leads to the Philadelphia chromosome

occurs when genetic mistakes cause breaks in the

middle of two vital genes located on chromosomes

9 and 22. They found that the break on chromosome 22 occurs in the middle of the bcr gene and

that the break on chromosome 9 occurs in the abl

gene. On the shortened end of chromosome 22,

the genetic rearrangement produces the abnormal

bcr-abl gene, the source of CML development. 

In 1986, Dr. David Baltimore and his research

group determined that, like the normal a b l gene, the

defective b c r-abl gene carries the code for a tyrosine

kinase, a class of proteins that plays an important role

in regulating cell growth and division. The normal

a b l gene will turn on or off, producing tyrosine kinase

to promote cell growth as needed. The aberrant b c ra b l gene, however, is always turned on and lacks the

critical piece that enables the gene to turn itself off.

As a consequence, b c r- a b l f l o ods the cell with the

instruction to divide constantly and also prevents the

leukemia cells from undergoing normal programmed

cell death or apoptosis, a process that helps to regulate white blood cell numbers. Several laboratories

confirmed the link between the defective gene and

CML through studies showing that the b c r-abl g e n e

was all that was needed to induce leukemia in mice.

Developing a Targeted Treatment 

During this same time period, advances in molecular

b i o logy were revolutionizing the field of drug discovery.

In the laboratories of Ciba-Geigy (later, Novartis), 

scientists were able to apply unfolding knowledge

about the workings of cellular pathways and communications systems in a number of drug development

76 The Nation’s Investment in Cancer Research

A Story of Discovery: Making the Connections for a

Targeted Cancer Treatment Takes Time and Perseverance
efforts. In one research program, scientists were looking for agents to inhibit protein kinases, a group of

cell signaling proteins that includes the Abl protein.

A number of such agents were found, including one

that they labeled STI571. 

1990M e anwhile, American oncologist Dr.Brian Druker was interested in determining how the Bcr-Abl protein, the product of the b c r- a b l

gene, fits into the complicated circuitry of cell signaling.

His research led him to believe that theB c r-Abl protein

could be a powerful target for a drug that could impede

the activity of the protein and be an effective t r e a t m e n t

for CML. When he learned about Ciba-Geigy’s complementary research, Druker asked scientists there for

candidate protein kinase inhibitors that he could test

against leukemia cells. At the end of 1993, the pharmaceutical company sent him several candidates,

including STI571. Druker screened the chemicals and

found that STI571 halted the growth of the leukemia

cells but had little effect on healthy ones. 

While this was an exciting outcome, there were still

many obstacles to overcome. The process of developing a new drug and getting it approved for use is lengthy

and expensive. Scientists must identify a possib l e

agent; study and test it for efficacy, pharmacology, and

toxicology; file with the Food and Drug

Administration; and finally evaluate it through largescale clinical trials. STI571 posed an additional business problem because the incidence of CML is quite

l o w, limiting the potential demand for the drug, and

two moderately effective treatments already were

available for CML, although both held potential for

serious side effects. 

Despite reservations, Novartis agreed to prod u c e

e nough STI571 for an initial clinical trial. 

D r. Druker began the Phase I trial, conducted to identify a safe dose level, in June of 1998. By December of

1999, he and his colleagues reported that white blood

cell counts for all of the 31 patients receiving a high dose

of STI571 had returned to normal, an effect that was

sustained for the eight months that the patients stayed

on the drug. In 9 of the 20 patients who were treated for

five months or longer, no leukemia cells could be found,

confirming that the drug was eliminating the source of

the cancer and with minimal side effects. Rarely are

such dramatic results seen in a Phase I trial.

2000In response to these exciting findings,Druker and his colleagues conducted a

larger study and reported in April 2001 that STI571

restored normal blood counts in 53 of 54 CML

patients, all of whom had resisted previous

c h e m o t h e r a p y. Of these patients, 51 were still doing

well after a year on the medicine, with most reporting

few side effects. Following “fast-track” review, the

F o od and Drug Administration approved STI571,

now known as GleevecT M, as a treatment for CML in

May 2001, beginning with patients not responding to

standard therapies.

The Story Continues

But the story of GleevecT M as a treatment for CML

is not complete. Patients receiving the drug need to

be followed for longer periods to determine whether

the positive effects will last and whether long-term

treatment can cause side effects. Unfortunately,

most patients with advanced disease relapse within

a year. The cause of resistance is now known, so scientists are trying to overcome it. Like most successful treatments, GleevecT M will undoubtedly spawn a

host of refinements. 

The story does not end with CML. In addition to

the Bcr-Abl signaling protein, the drug appears to target two other protein kinases, the c-kit receptor and

the PDGF receptor. The c-kit receptor is active in

gastrointestinal stromal tumor (GIST) and the PDGF

receptor associated with many types of cancer,

including a form of brain cancer called glioblastoma.

NCI-supported and private-sector scientists are

investigating the effectiveness of GleevecT M a g a i n s t

cancers of the breast, ovary, and lung. See page 31 for

more information.

The success of GleevecT M offers substantial hope

that molecular targeting can be a highly effective

strategy to thwart the growth of specific cancers. It is

likely that GleevecT M is the first of many potent, but

s a f e r, targeted preventive and treatment drugs to be

developed as a result of advances in our understanding of cancer at the molecular level.

Story of Discovery 77
78 The Nation’s Investment in Cancer Research

4

E x t ra o r dinary Opportunities for Inv e s t m e n t

Molecular T a rgets of Prevention and Tr e a t m e n t

THE OPPORTUNITY

W

e are entering an era in cancer research that

holds the potential for an exciting new

approach to drug development for cancer prevention

and treatment. These drugs will be designed to target

specific molecular features of cancer cells, such as

small but critical errors in genes or proteins that lead

to tumor growth. By selectively attacking cancer

cells, these revolutionary agents promise to be less

toxic and more effective than current drugs. This

extraordinary opportunity of molecular targeting has

been generated by knowledge gained through recent

advances in multiple research disciplines from basic

cancer biology to synthetic and biosynthetic chemi s t r y.

Our ability to treat cancer is integrally linked to

our understanding of cancer. Historically, using available technology scientists could tell by features such

as the shape or size of the cell whether it was cancerous, but not why it was cancerous or

how its inner workings might differ

from normal cells. Yet investigators

applied what they could see to prod u c e

the drugs now in use that, alone or with

surgery or radiation, can cure some cancers and ease symptoms in others.

H o w e v e r, these drugs tend to be n o n -

s e l e c t i v e – while treating the cancer they

also attack a number of healthy cells.

C o n s e q u e n t l y, cancer chemotherapy is

often accompanied by a variety of sometimes devastating short- or long-term side effects. It

has also been hard to pinpoint why many tumors do

not respond well to available drugs.

Scientists are now harnessing recent advances in

technology to learn more about the nature of cancer

a n d to identify ways that cancer cells differ from

healthy cells at the molecular level. This knowledge

creates the potential for cancer drugs that target these

differences to more effectively attack the cancer while

sparing healthy tissues. To harness this potential w e

need to create better ties between laboratory and

clinical research to integrate drug discovery, development, and clinical testing. In this cooperative setting

researchers can effectively identify molecular targets

in the cell, find drugs that will “hit” the targets, test

these drugs for safety and efficacy in the laboratory

and in animal studies, and test the use of successful

candidate drugs in clinical trials. Ultimately these

drugs will be used by health care providers to more

effectively prevent and treat cancer, with far fewer

side effects.

PROGRESS IN PURSUIT OF OUR GOAL 

T

he NCI is advancing the molecular targeting

approach to drug discovery through a number of

exciting initiatives. 

Identifying and Validating Molecular

Targets for Drug Discovery

Through the Molecular Target Drug

Discovery (MTDD) program investigators are identifying novel molecular targets, validating these targets as sites that

can be exploited for cancer therapy, and

developing tests that determine how

well potential agents work on these targets. The 41 research groups currently

supported are studying a number of

molecular targets. One group of scientists is investigating Bcl-xL, an aberrant

protein that enables cancer cells to

evade apoptosis, or programmed cell death – a process

that normally eliminates damaged cells from the

b od y. Another group is investigating Heat Shock

Protein (HSP) 90, a “stress response” protein that is

overexpressed in tumors and may play an important

role in cancer growth. Still another team is studying

how DNA methylation can lead to cancer.

Methylation is a specific type of chemical alteration

that can prevent or reduce the expression of affected

genes. Researchers have found that in some cancers

DNA repair genes and tumor suppressor genes are

78 The Nation’s Investment in Cancer Research

G O A L

Accelerate disco very,

development, and testing

of pr evention and 

treatment agents that 

target the molecular

changes of cancer .
silenced by this mechanism and unable to do their

job in preventing cancer. 

Resources for Exploiting Molecular

Targets for Drug Discovery

The Molecular Targets Laboratories (MTLs) w a s

first funded in FY 2002 to capitalize on the opportunities emerging from advances in genomics, molecular

b i o l o g y, combinatorial chemistry, informatics, and

imaging. Through this initiative scientists are applying

advances to create a resource of biological assays and

chemical probes to study cancer-related targets. This

work enables biological studies of cancer, including

physiological and biochemical monitoring, and provides a platform for drug discovery.

Through the Mouse Models of Human Cancers

C o n s o r t i u m groups of academic researchers have created and are making available to researchers mice with

defined genetic alterations that predispose the animals

to certain types of cancer. Six strains were available as

of 2001, and up to 30 more may be added annually.

These models could serve as a basis for testing n e w

molecular targeting treatment and prevention strategies. As more models are added, it will be possible to

create subsequent generations of mice with more than

one genetically defined alteration to resemble human

tumors even more closely. Academic members of the

consortium are developing ties to pharmaceutical

industry sponsors to facilitate the testing and evaluation of new compounds in these mouse strains. For

more information about this initiative, see page 58. 

We are working with the National Institute for

General Medical Sciences on the National Beam

P r o g r a m to provide technology to quickly identify

the structure of important molecular targets in cancer

cells and efficient computer modeling to identify

potential anti-cancer agents suited to “hit” the targets

based on these structures. Partners are constructing

“the x-ray beamline” at the Argonne National

Laboratories. This cutting-edge technology will

greatly improve scientists’ ability to determine the

complex structure of proteins and larger multi-molecular complexes. 

Identifying Compounds That Hit the

Targets

Through several NCI initiatives, chemists and biologists are collaborating to create libraries of synthetic,

biological, and natural compounds that will be tested

for therapeutic potential against validated molecular

targets. These scientists are developing “smart”

assays, or tests used to screen the compounds to identify those that “hit” defined target molecules. 

The National Cooperative Drug Discovery

Groups program supports innovative, multidisciplin a r y, multi-project approaches to discover new 

anticancer treatments. Thirteen funded groups are

progressing in a variety of areas, including an innovative effort to design and evaluate novel anti-cancer

drugs that inhibit the enzyme geranylgeranyltransferase I (GGTase I). This enzyme is involved in

activating a cellular pathway involving the Ras

oncogene, which has been implicated in a number

of human cancers. Researchers hope to identify an

agent that will selectively suppress GGTase I and

the cancer-promoting activity of the Ras pathway.

This research is an excellent example of how a basic

discovery generated through an NCI grant can be

expanded into clinical development with support

from special NCI initiatives.

In Biology-Chemistry Centers m u l t i d i s c i p l i n a r y

teams of scientists use a combination of chemical and

biological techniques to create libraries of chemically

diverse structures with potential anti-cancer effects.

Using “smart” assays, scientists screen the compounds

to identify those that will interact with cancer- s p e c i f i c

molecular targets. The six teams funded through this

initiative have screened hundreds of thousands of compounds for anti-cancer activity. Promising compounds

include the newly designed GFB-111 molecule. T h i s

novel molecule binds to growth factors — proteins

that help to regulate new tissue growth — and has

been shown to significantly inhibit new blood vessel

formation (angiogenesis), and thereby growth of

human tumors studied in mice. 

NCI supports the collection of natural extracts

from plants throughout the world. Using highthroughput screening, scientists are testing these

extracts for use either as targeted cancer drugs or as

probes to study targets in the cell. One chemical,

Halichondrin B, which occurs naturally in a Pacific

Ocean sponge, has been found to have considerable

anti-tumor activity. Because of the scarcity of

Halichondrin B in its natural form, researchers have

started designing promising synthetic analogs. Tw o

such analogs have shown significant anti-tumor

activity against human breast, colon, melanoma, and

ovarian tumors grown in laboratory animals and will

next be studied for clinical usefulness. 

The Rapid Access to NCI Discovery Resources

Extraordinary Opportunities 79
80 The Nation’s Investment in Cancer Research

THE PLAN — MOLECULAR TARGETS OF PREVENTION AND TREATMENT

Goal

Facilitate the expanded exploration of the causes of cancer and the discovery and development

of agents that specifically “target” these causes to treat and prevent cancer.

Objectives and Milestones for Fiscal Year 2003

1. Identify, characterize, and validate the combinations of deregulated cellular proteins and

pathways that cause cancer in precancerous and cancerous cells. 

■ Through the Molecular Target Drug Discovery Grants (MTDD), increase support for research

to identify cellular targets and discover related anti-cancer agents. Continue support for the

MTDD Grants and previously awarded Biology-Chemistry P01s. Provide screening assistance

and informatics management. $6.00 M

2. Determine the cancer-causing deregulated pathways that can be targeted by prevention

or treatment agents. 

■ Amplify support for the Molecular Target Laboratories to bolster the systematic search for new

preventive and therapeutic agents. 1) Develop assays to identify possible treatments for cancer

and 2) acquire large libraries of natural and synthetic compounds. $5.00 M 

■ Support the Mouse Models of Human Cancers Consortium to accelerate the pace of making

available accurate, reproducible mouse models of human cancers. $1.00 M

3. Provide the infrastructure for researchers to develop assays to test large numbers of

potential drugs against validated “drugable” deregulated proteins and pathways.

■ Expand support for the National Cooperative Drug Discovery Groups. $5.00 M

■ Expand the availability of NCI discovery resources to academic laboratories through the Rapid

Access to NCI Discovery Resources program (RAPID). $1.00 M

■ Expand efforts to collect, inventory, and distribute diverse compounds — synthetic chemicals,

natural products, and biological materials, and provide informatics support for anti-cancer

research. $3.00 M

■ Develop a translational research program to closely link molecular imaging, cancer signatures

and molecular targets. This would allow serial imaging and serial biopsies used to assess

genomics and proteomics , to be coupled with therapeutic interventions which use systemic

agents, radiation therapy, immunologic treatment and chemopreventive agents. The ability to 

$6.0 M

$6.0 M

$15.0 M

(R*A*N*D) is a new program that expedites the

development of drug research capabilities in academic institutions. R*A*N*D focuses on laboratorybased studies that are the starting points for new drug

development, supporting early formulation, pharmacokinetic, pharmacology, and toxicology studies.

R*A*N*D assists in the development of highthroughput laboratory assays to screen large numbers

of promising chemicals. The program supports the

development of libraries of chemicals that scientists

can draw upon for study. One of the five initial

R*A*N*D projects uses microarray technology to

study molecular profiles of leukemia cells and to identify more targets. Another exciting project is creating a library based on a compound that targets an

important cellular protein involved in angiogenesis, or

generation of new blood vessels – an integral component of tumor growth. 
Extraordinary Opportunities 81

conduct multiple studies will provide a robust data set to understand the biology behind the

image needed to credential new molecular targets. $3.00 M

■ Support an intramural Molecular Targets Drug Discovery Program to develop screening assays

for biomolecules that interact with molecular targets, conduct screens to test candidates for

probes and inhibitors of molecular targets, characterize and validate compounds that hit the

targets, and facilitate development of needed research chemicals as well as promising molecular

target compounds. Support the isolation, purification and characterization of individual components of natural products extracts. $1.00 M

■ Develop a clinical proteomics initiative to use laser capture microdissection of human tissue

specimens and to develop new laboratory tools, including a new protein array, 2D-PAGE, signal pathway profiling, and SELDI-TOF protein pattern fingerprinting for clinical proteomic

applications in human cancer and drug toxicity detection. $2.00 M

4. Facilitate the steps necessary to turn a target-specific lead compound into a clinical agent. 

■ Expand support for the Rapid Access to Intervention Development (RAID) program. $3.0 M

■ Increase funding to RAPID to develop prevention agents from the laboratory through clinical

trials of efficacy. $1.0 M

■ Expand assistance to small businesses through Flexible System to Advance Innovative

Research. $3.0M

5. Investigate the use of novel combinations of radiation therapy with molecular therapeutics. 

■ Support individual investigators and industry to develop treatment programs using new

agents with radiation therapy. Facilitate collaboration with industry and individual investigators and establish a system for alerting clinical investigators when agents are ready for clinical trials. $ .50 M

6. Fund Clinical Trials Networks that will take drug candidates into human trials designed

to test whether or not the drug is working against the intended target and is affecting

the progression of the cancer in the intended manner .

■ Widen support for the Interdisciplinary Research Teams for Molecular Target Assessment

program. $2.0 M

Management and Support

To t a l

$7.0 M

$ 0.5 M

$2.0 M

$6.0 M

$42.5 M

NCI provides, at no cost, samples of synthetic

chemicals, collected natural products, and biological

m a t e r i a l s to investigators who want to screen them

against molecular targets. NCI has made available

more than 140,000 synthetic chemicals, 80,000 natural products extracted from plants and marine organisms, and a variety of biological agents for use in studying the compounds.

Turning Promising T a r g e t - D i r e c t e d

Compounds into Drugs for Human Use

Translating laboratory discoveries into agents for human

use is an exacting task that requires very spec i f i c, 

interrelated activities. For example, sufficient quantities of the drug must be made for formulation, stab i l i t y, and safety testing. Drug optimization and

development studies enable scientists to determine

the manner and amount of drug to be delivered based
on a drug’s overall effect on an animal. NCI is supporting this critical arm of drug development through

a variety of initiatives.

The Rapid Access to Intervention Development

( R AID) program provides preclinical drug development resources to academic institutions in 50 current projects. Two interventions developed through

RAID are now being tested in clinical trials. One

intervention is a novel gene therapy approach that

delivers a pair of therapeutic “suicide genes” to

prostate tumors, thereby rendering malignant cells

sensitive to specific drugs and radiation. The other

is the anti-cancer agent 6-Diazo-5-Oxo-lNorleucine (DON), which selectively inhibits

growth of neuroendocrine tumor cells. As many as

nine additional agents will be in clinical trials testing by the end of 2001.

The Rapid Access to Preventive Intervention

Development (RAPID) program provides preclinical

and early clinical drug development resources to academic investigators who are developing novel agents

to prevent, reverse, or delay cancer development.

The seven projects currently funded through RAPID

include studies to develop certain marine-derived

p r oducts as chemopreventive agents, a human papillomavirus vaccine, and work to determine the preventive effects of certain proteins.

The Drug Development Group provides support

for academic and corporate-derived compounds

when NCI is responsible for conducting and monitoring the drug’s clinical development. A number of

promising agents have been developed through this

program. PS-341, a novel compound presented to

NCI by Millennium Pharmaceuticals, is the first in a

new class of agents that take aim at a new cellular 

target — the proteasome enzymes. These enzymes

play an important role in the breakdown of proteins

that regulate the cell cycle. PS-341 inhibits the

breakdown of these proteins and leads to cancer cell

suicide. In preliminary clinical trials, PS-341 

p r oduced promising effects in both multiple myeloma

and prostate cancer patients. NCI and Millenium are

pursuing further clinical testing. 

Certain cancer-causing genes induce cancer when

they block the normal expression of healthy genes.

Histone deacetylase inhibitors relieve this suppression. In cooperation with extramural organizations,

NCI has studied the anti-tumor effects of several such

inhibitors, including pyroxamide, an inhibitor identified by scientists at an NCI-supported Cancer Center

as a candidate for drug development. Pyroxamide

considerably reduced tumor growth in animal mod e l s

of breast, lung, and prostate cancer without causing

t o x i c i t y. Preliminary clinical trials are now underway

at the Cancer Center. 

The Flexible System to Advance Innovative

R e s e a r c h (FLAIR) provides funds to small businesses

to develop cancer therapeutic and prevention agents

from basic discovery to clinical trials. There are currently 20 active FLAIR grants, including an investigation of a potential anti-cancer agent, PX-12. This

agent targets thioredoxin, a cellular protein that is

overexpressed in a number of human cancers and

associated with aggressive tumor growth and poor

patient prognosis. PX-12, which inhibits the growthpromoting activities of thioredoxin, has shown potent

anti-tumor activity against leukemia, breast, and lung

cancers in animal models. Phase 1 clinical trials supported by the FLAIR program are now under way. 

The R a d i a t i o n Modifier Evaluation Module

( R AM E M ) program will serve individual investigators

and industry in the design and development of treatment programs for the use of novel molecular, biologic, and cytotoxic agents in conjunction with radiation

t h e r a p y. Integration of molecular imaging, molecular

signatures, and molecular therapeutics with radiation

therapy is a high priority of NCI’s Intramural Program

because many new anti-cancer agents may ultimately

be used in combination with radiation therapy. 

Developing Clinical Trials Programs T o

Study New Molecular Target Agents

The Interdisciplinary Research Teams for Molecular

Target Assessment ( I RT M TA) is a new program that

enables interdisciplinary teams of scientists to develop

molecular assays, molecular and cellular imaging

probes, and other tools to assess the effects of targeted interventions in preclinical models and in early

clinical trials. The teams will study critical biological

processes to uncover high-priority targets for cancer

prevention or treatment and drug discovery. The first

set of applications for this program was funded in

early 2001.

82 The Nation’s Investment in Cancer Research
THE OPPORTUNITY

T

he devastating impact of tobacco use and tobacco

smoke exposure on the incidence of cancer, heart

disease, and stroke is both compelling and conclusive .

Tobacco use causes more premature death than do all

drugs of abuse combined. Lung cancer, which is estimated to account for approximately 157,400 deaths

in 2001, would be a rare disease in the absence of

smoking. Cancers of the mouth, pharynx, larynx,

esophagus, pancreas, cervix, kidney, and bladder are

all associated with tobacco use.

A major challenge in the fight against tobaccorelated cancers is that addiction to nicotine drives the

continued use of tobacco even when the user is fully

aware of increased risk of disease and premature

death. Some people will continue to smoke even as

they undergo treatment for a life-threatening disease. Furthermore, tobaccorelated diseases such as lung cancer

remain some of the most difficult to

treat effectively.

We need to better understand the

genetic, biological, behavioral, and

social influences that explain:

■ Why children and adults use tobacco.

■ How they become addicted.

■ Why those who become addicted

have such difficulty quitting. 

■ How to prevent, detect, and treat cancers caused

by exposure to tobacco and its constituents. 

N C I ’s commitment to preventing, diagnosing, and

treating tobacco-related cancers began more than 40

years ago and remains one of our highest priorities. Our

research has benefited individuals and has improved the

p u b l i c ’s health. To remain at the leading edge of this

important area of research, NCI must devote additional resources to address the complex challenges of

tobacco use and tobacoo-related cancers.

PROGRESS IN PURSUIT OF OUR GOAL

T

he NCI has a unique role in supporting the entire

range of tobacco research, from understanding why

and how people use tobacco to developing and evaluating more effective treatments for nicotine addiction

to detecting and treating tobacco-related cancers and

metastatic disease. NCI has a special concern for the

health of former smokers, people who followed advice

to quit smoking, who now comprise about half of those

diagnosed with lung cancer. The breadth of NCI’s

support is reflected in our investments both in basic

biological research on the effects of tobacco exposures

and in community-based studies of smoking prevention and cessation programs. 

Recent advances in knowledge about tobacco use

and tobacco-related cancers provide an unprecedented opportunity to reduce the disease burden from tobacco. New evidence is

helping to better explain why some people are more vulnerable than others to

DNA damage caused by tobacco exposure. Research on the early detection of

lung cancer suggests that it may soon be

possible to identify cancers in smokers

and former smokers at a much earlier and

more treatable stage. Recent studies of

teen smokers have identified psychological factors that increase the risk of becoming addicted, as well as the need to provide younger smokers

with specialized programs to help them quit. A new

evidence-based guideline, which NCI helped to

develop, enables healthcare providers to offer smokers

practical, effective strategies to quit smoking. If

applied widely, this could have a dramatic effect on

the number of smokers who successfully quit. Also,

new cancer treatments based on molecular targeting

provide models for how to increase the effectiveness

of therapies for tobacco-related cancers. 

The following are examples of research initiatives

underway related to the objectives of the Research on

Tobacco and Tobacco-Related Cancers Opportunity.

Extraordinary Opportunities 83

5

E x t ra o r dinary Opportunities for Inv e s t m e n t

R e s e a r ch on Tobacco and Tobacco-Related Cancers 

G O A L

Understand the causes o f

tobacco use, addiction,

and related cancers and

apply this knowledge to

their pr evention and 

treatment.
84 The Nation’s Investment in Cancer Research

THE PLAN – RESEARCH ON T O BACCO AND T O BAC C O - R E L A TED CANCERS

Goal

Understand the causes of tobacco use, addiction, and tobacco-related cancer and apply this

knowledge to their prevention and treatment. 

Objectives and Milestones for Fiscal Year 2003

1. Expand efforts to define the biological, behavioral, and social bases of tobacco use and

addiction.

■ Initiate prospective observational studies of the quitting and relapse process, including the

effectiveness of medications. $4.00 M 

■ Improve understanding of the social bases of tobacco use by supporting studies of economic,

geographic, sociocultural, and policy-related factors. $2.00 M

■ Continue support for including questions on tobacco use in the Current Population Survey.

$2.00 M

■ Support analytical tools, resources, and analyses of existing and new tobacco use data. $5.00 M 

■ Expand collaborative efforts aimed at the translation of research findings on the determinants

of tobacco use to clinical and community intervention research. $4.00 M

2. Accelerate progress in understanding the interplay among tobacco, other exposures such

as alcohol and asbestos, and host susceptibility on cancer risk. 

■ Support clinical and population studies that include tissue and biospecimen resources to investigate the genetic, biological, and behavioral factors influencing vulnerability to smoking

dependence and tobacco-related cancer. $6.00 M 

■ Integrate biospecimen collection into screening trials to better understand the molecular basis

of early-stage lung cancer. $6.00 M

■ In collaboration with other Federal agencies, synthesize the latest evidence regarding environmental tobacco smoke and identify critical directions for new research. $1.00 M

■ Support studies of the mechanisms of susceptibility to tobacco-related cancers to understand

the effects of specific forms of tobacco and types of tobacco exposure. $5.00 M

$17.0 M

$22.0 M

Preventing, T reating, and Screening for

Tobacco-Related Cancer s

Lung cancer studies are the focus of much of our

research on tobacco-related cancers and may be

applicable to other cancers as well. 

■ A chemoprevention and biomarker study involving lung cancer survivors and patients at high risk

for lung cancer is underway. Strategies include the

use of drugs, vitamins, or other agents to reduce the

risk or delay the development or recurrence of canc e r. Investigators in the Lung Cancer Biomarkers

and Chemoprevention Consortium began recruiting patients in the summer of 2001 to participate

in two trials evaluating chemopreventive drugs.

Researchers will perform biomarker analyses on tissues obtained during the studies and correlate

these findings with patient outcomes. 

■ The Lung Cancer Screening Study began in 2 0 0 0

to assess the feasibility of the spiral computed

tomography (CT or CAT) scan to detect early lung

cancers. As of the spring of 2001, 3,300 people

were randomized to either a spiral CT or a chest 

x-ray at six screening centers across the country.

I n v e s t i g ators are comparing the lung cancer detection rates; measuring how much and what kind of

medical follow-up is needed; and tracking how 
Extraordinary Opportunities 85

■ Integrate the use of mouse models into research on the development of tobacco-related cancers

to identify the relative contributions among the genes related to susceptibility and resistance

and other endogenous and exogenous factors. $2.00 M 

■ Facilitate scientific collaborations between lung and head and neck cancer SPORE investigators and TTURC investigators to better integrate biological, pharmacological, and behavioral

research on tobacco use and its impact on disease. $ 2.00 M

3. Develop, test, and disseminate more effective interventions to prevent and treat tobacco

use and tobacco-related cancers, especially in high-risk individuals and groups.

■ Support the development of biomarkers of tobacco exposure and risk through collaborative

work with National Institutes of Health laboratories and those at the Centers for Disease

Control and Prevention’s National Center for Environmental Health. $2.00 M 

■ Provide supplements to the Transdisciplinary Tobacco Use Research Centers,

State/Community Tobacco grants, and Cancer Centers to stimulate health disparities research,

including clinical assessment and care of tobacco-related cancers, differential tobacco use, and

quitting patterns. $4.00 M

■ Support collaboration with public and private tobacco research funding organizations to identify and disseminate successful tobacco use prevention interventions. $3.00 M

■ Support the development of NCI’s new tobacco treatment and research clinic to speed the discovery and testing of new treatments. $1.00 M

■ Accelerate the identification of new treatments for nicotine addiction through the creation of

an NCI/National Institute on Drug Abuse drug development and clinical trials collaborative.

$2.00 M

■ Support research on smoking cessation and relapse prevention in cancer patients and survivors.

$2.00 M

■ In order to accelerate the development of new, molecularly based treatments for lung cancer,

support a molecular defects database, a tissue resource, and improved exposure assessments to

enable more sophisticated studies of treatment outcomes. $10.00 M

Management and Support

To t a l

$24.0 M

$4.0 M

$67.0 M

frequently participants receive spiral CT scans outside the study. Although spiral CT scans are advertised as a new way to find early lung cancer in both

current and former smokers, questions remain unanswered regarding its risks and benefits making these

results crucial for the design of larger, more definitive studies. The study builds on the infrastructure

of the NCI-supported Prostate, Lung, Colorectal,

and Ovarian screening trial , launched in 1992. 

■ T hrough two new initiatives begun in the summer

of 2001, NCI will fund preclinical and clinical studies to identify newer, more potent agents that may

prevent cancers in former smokers . Currently,

almost half of all new cases of lung and bladder cancer occur in former smokers. It is vitally i m p o r t a n t

to identify molecular and imaging markers of cancer risk and abnormal and uncontrolled cell

growth and to test agents that can prevent the

development of cancer in this group. 

Understanding the Interplay Among

Tobacco, Other Exposures, and Cancer

While costly, resource-intensive, and long, cohort

studies that include genetic and biomarker components are invaluable tools for collecting large

amounts of information critical to understanding
86 The Nation’s Investment in Cancer Research

cancer risk and assessing exposures to carcinogens

prior to cancer diagnosis. 

■ T h e Prostate, Lung, Colorectal, and Ovarian

s c r e e n i n g trial is examining emphysema in relation to smoking, how genetic factors influence

smoking, and the differences between current and

former smokers regarding genes that might be

involved in nicotine dependency. This information will prove increasingly precious over time as

cancer cases develop in the cohort and their

biospecimens become available for special study.

■ T h r o ugh an NCI-supported study of a group of

women in Shanghai, we have an unprecedented

opportunity to prospectively collect data and

biospecimens from both non-smoking women who

are exposed to second-hand smoke and their husbands who tend to be active smokers. Similarly, we

have incorporated major biospecimen collections

into studies that compare groups of people with cancer to healthy control groups. Specific studies initiated during the past year focused on smoking-related cancers such as lung, bladder, and renal cancers. 

■ NCI supports regional biorepositories, such as the

expanded Frederick Biorepository and the

Cooperative Human Tissue Network , which fill a

critical need by housing and maintaining human

biospecimens such as tissue, blood, and urine.

Scientists collect these biospecimens from largescale studies and make them available to

r e s e a r c h e r s .

Understanding and Pr eventing Youth

Tobacco Use

Tobacco use arises from a variety of influences,

including social factors such as peer and parental

smoking, as well as biobehavioral and genetic factors.

Because the majority of smokers begin using tobacco

before the age of 18, understanding why youths use

tobacco is a high priority for NCI. 

We have substantially expanded our support for

studies that test ways to prevent tobacco use among

the young and to help users quit . NCI, in collaboration with other NIH institutes, is now supporting

more than 50 research grants related to the prevention, dependence, and cessation of adolescent tobacco use. This wealth of cutting-edge research is beginning to yield new insights into youth tobacco use. In

June 2001, NCI brought together more than 200

investigators from across the country to share the latest scientific evidence concerning tobacco use among

youth. Their research indicates that both social

influences and inherited factors are predictors of

youth tobacco use. 

■ A recent study of fifth- and eighth-grade students

from New England middle schools showed that

students who view more tobacco use in movies are

more likely to try smoking. 

■ Studies of twins show that inherited factors influence whether a person will smoke and how difficult it will be to quit. 

O ngoing research supported through the

Transdisciplinary Tobacco Use Research Centers

(TTURCs) is beginning to provide information on

youth tobacco use. NCI, the National Institute on

Drug Abuse (NIDA), and the Robert Wo od Johnson

Foundation (RWJF) funded seven TTURCs at U.S.

academic institutions in 1999. Each organized around

a special theme, these centers have yielded significant

research results.

86 The Nation’s Investment in Cancer Research

Tobacco and Tobacco-Related Cancers: 

Good News and Bad 

The Good News

■ C o m p re he nsive state/community tobacco cont rol pro g ra ms work. For exa m p l e, Arizona ’ s

a dult tobacco use dropped from 23 perc e nt in

1996 to 18 perc e nt in 1999. 

■ S mo kers do want to quit. Approx i mately 39

p e rc e nt of all adult smo kers ma de an attempt

to quit in the past year.

■ C o ns u m p t ion of cig a rettes cont i nues to de c l i ne,

dro p p i ng from 4,345 per capita in 1963 to

2,146 per capita in 1999.

■ L u ng and bro nc hus cancer de a t hs are estima t e d

to drop from 158,700 in 1996 to 157,400 in

2001, primarily due to de c reased smo k i ng .

The Bad News

■ Youth smo k i ng inc reased from 28 perc e nt in

1991 to 35 perc e nt in 1997 although it has

s i nce de c l i ned some w h a t .

■ T hose with the least educ a t ion and inc o me

s mo ke the most: 11 perc e nt of college gra duates smo ke compared with 34 perc e nt of tho s e

w ho did not finish high school. 

■ L u ng cancer now kills approx i mately 157,000

people each year in the U.S. alone. It would

s e l dom occur if people did not smo ke.
■ TTURC research has shown that smokers with a

unique genetic makeup started smoking almost two

years earlier than others. Investigations of genes

important in smoking have focused on the

dopamine system and on the brain chemical serotonin, which plays a role in depression and anxiety,

both traits associated with smoking.

■ Another study has assessed factors associated with

high school students’ decisions to smoke. High academic performance, perceived academic competence, and involvement in school-related clubs and

sports teams were found to decrease the risk of smoking, while alcohol or marijuana use and noveltyseeking were associated with increased smoking. 

■ Another TTURC study is examining factors that

affect the progression of smoking initiation and use

among youth of diverse cultures. Early results of this

research suggest that the patterns of smoking initiation in the United States and China are similar and

that the optimal age for smoking prevention interventions is between 10 and 15, earlier than many of

the programs aimed at youth currently start.

Treating Tobacco Dependence

Smoking cessation remains among the most costeffective approaches to reducing cancer risk, but

despite the dramatic advances in understanding the

nature of nicotine dependency during the past

decade, the best treatments are effective for less than

a third of all smokers who try to quit. NCI continues

to support effective behavioral, pharmacological, and

community treatment approaches . 

■ Understanding the genetic factors related to nicotine initiation and dependence will be critical to

the development of new medications to help

smokers quit. With NIDA, NCI created a working group to advise both Institutes on key areas

where progress can be achieved in the development of new medications for smoking cessation. 

■ N C I has supported innovative smoking cessation

interventions that are tailored to the unique needs

of individual smokers. For example, one recent

study found that an “expert system” intervention,

which provided computer-assisted feedback and

help, resulted in quit rates that were almost 33 percent higher than for those without it. Conducted in

a health care system, this study opens the door for

increased assistance to smokers in environments

where maximum medical follow-up is possible.

■ A recent study funded through the NCI SPOR E s

initiative showed that those smokers who carried

the DRD2-A1 genotype were more likely to

relapse than those who carried the DRD2-A2

genotype, suggesting the possibility of developing

tailored approaches to treatment that take into

account unique genetic traits. (See p. 24.)

Smokers who do not wish to quit or who are unable

to do so comprise a target market for the tobacco and

pharmaceutical industries. The tobacco industry is

developing and marketing new products intended to

reduce the harm of continued smoking. The pharmaceutical industry is developing medications for smoking reduction, along with those for cessation.

Nevertheless, there is little evidence to suggest that

changing tobacco products or using medications for

smoking reduction will result in decreased harm.

Extraordinary Opportunities 87

International Eff o r t s

Our efforts to address tobacco cont rol in the

United States clearly can inform and be info r me d

by re s e a rch conducted in other count r ie s. Of part icular int e r na t io nal importance are surveillance of

t he chang i ng global patterns of tobacco use,

de v e l o p me nt of scie nt i f ic and public health ne tworks to optimally address tobacco cont rol, and

de v e l o p me nt of int e r v e nt io ns for pre v e nt i ng and

t re a t i ng tobacco use. In support of global tobacco

re s e a rch effo r t s, NCI has:

■ Pa r t ne red on a Global Youth Tobacco Survey led

by the Centers for Disease Cont rol and

P re v e nt ion to do c u me nt and monitor the pre v al e nce of and cont r i b u t i ng factors of youth

tobacco use.

■ C o ntributed to the de s ign and fund i ng of a ne w

re s e a rch initiative led by the NIH F o g a r t y

I nt e r na t io nal Center that will support int e r nat io nal tobacco and health re s e a rch as well as

c a p a c i t y - b u i l d i ng efforts and stud ies that

emphasize tobacco cont rol re s e a rch in low- and

m idd l e - i nc o me count r ie s.

■ I n i t iated a new lung cancer study in Milan,

It a l y, to evaluate ge ne - e n v i ro n me nt int e ra ct io ns in the de v e l o p me nt of lung canc e r. This

s t udy inc l udes the ge ne t ics of nic o t i ne add ict ion and the tre a t me nt of smo k i ng de p e nde nc e.
88 The Nation’s Investment in Cancer Research

6

E x t ra o r dinary Opportunities for Inv e s t m e n t

Cancer Communications

THE OPPORTUNITY

I

t is not unusual today for newly diagnosed cancer

patients to go to their doctors’ appointments

armed with printouts from CancerNet or other We b

sites and lots of questions. People have more ways

than ever to get information: by telephone, fax,

email, the World Wide Web, TV and radio, and in

person. And the future holds even more choices:

automated monitoring of vital signs, voice recognition software, wider use of wireless technology, and

other technologic advances to make it easier and

faster for people anywhere to access the best information about cancer. 

N C I ’s opportunity is to optimize the

use of these tools while enhancing the

absolutely essential interaction of

patients with their doctors and nurses.

Indeed, new communication tools can

facilitate partnerships between patients

and their physicians. We must push

forward the frontiers of technology in

support of the public, patients, their

families, and medical teams to ensure

access to individualized, high quality,

NCI-validated information. From primary prevention to survivorship and end-of-life

issues, communication empowers people to make

informed cancer-related decisions and to engage in

behaviors that will improve their health. 

To build on our progress in refining health communication theories and interventions, we must close

major gaps in our understanding of how people access

and use health information as well as the discrepancies between what is known and what is practiced.

We must: 

■ Provide accurate and balanced information about

all areas of cancer prevention, diagnosis, treatment, and care. 

■ Learn how to help people distinguish important

health risks from insignificant ones and make

informed choices despite exposure to contradictory or inaccurate health messages. 

■ Inform healthcare providers of emerging best

practices, help them become more effective communicators, and integrate communications into

all aspects of cancer care. 

■ Find and implement the best ways to disseminate

research results to the cancer research community,

medical practitioners, patients, individuals at risk,

and the public.

■ Increase communication with patients about access

to and participation in high quality clinical trials. 

■ Reduce cancer-related health disparities through

health communications research and activities.

■ Expand the cadre of health communications scientists and practitioners who conduct research

and apply results. 

Through these efforts, we will gain a far

richer understanding of how people use

health information and access communications technologies of all kinds. We

will use that understanding to improve

outcomes in cancer prevention, early

detection, and treatment and to

improve the lives of cancer survivors

and patients needing palliative care.

88 The Nation’s Investment in Cancer Research

G O A L

Understand and apply 

the most effectiv e

communications

approaches to maximize

access to and use o f

cancer information by all

who need it. 

Study Shows P e rceptions Can Change 

NCI-supported researchers have shown that the

combination of tailored print materials and a call

from a telephone health advisor can have several

positive effects. This was the first study to show

that women’s perceived risks about breast cancer

could be changed, and that the changes were

maintained a year later. Women who received the

combination of tailored communications also

were more knowledgeable about breast cancer and

mammography and were significantly more likely 

to get mammograms.
Extraordinary Opportunities 89

PROGRESS IN PURSUIT OF OUR GOAL 

T

o maximize the effectiveness of all our communications and to support communications research,

planning, implementation, and evaluation, we are

taking steps to collect, more effectively analyze, and

disseminate critical information about our audience

g r o u p s. Planning for the Health Information

National Trends Survey (HINTS) is well underway.

HINTS, to be launched in 2002, will be the only

national survey focused on cancer communications.

It will gather information from about 9,000 participants on health, sociodemographics, and access to

health care; knowledge about cancer; risk perceptions; cancer-related behaviors such as cancer prevention and screening; as well as data on such topics as

personal cancer experience, social ties, and self efficacy.

The data will be analyzed and made quickly available to

the research community to inform future communications research and program planning for cancer as well

as other health issues. Data will also be shared with the

advocacy community through briefings and special

r e p o r t s .

NCI staff are tapping a health and lifestyle information database to identify and disseminate data on

the information needs of specific audiences, develop

appropriate educational messages, and identify the

best media, locations, and techniques for communicating cancer information. Staff also have developed

and maintain a NewMediacy listserv that is narrowing the knowledge gap between the private and public sectors. 

NCI-sponsored pilot projects and educational

materials focus on increasing access to and use of

cancer communications by all populations. Last year,

NCI announced a new initiative and within the same

fiscal year, funded four research and development projects to develop unique approaches for overcoming the

cancer digital divide. The projects provide underserved groups with access to and the wealth of cancer

information now available through computers. Each

involves public-private partnerships, and one has

resulted in a joint effort with the Markle Foundation

for continued funding. (See the sidebar on this page

for more information.) 

NCI also is developing a communications toolkit to

guide the development of health communications

programs for underserved communities. It is designed

to assist leaders and organizations in promoting health

NCI Supports Digital Divide Pilot Pr o j e c t s

NCI is supporting four re s e a rch and de v e l o p me nt

p rojects to overc o me the digital divide by testing

t he efficacy of new commu n ic a t io ns techno l o g ies in

c a ncer pre v e nt ion and educ a t ion. These pro j e c t s

involve partnerships amo ng NCI-supported Canc e r

C e nters and Cancer Info r ma t ion Service (CIS) Cent e r s

at universities and a wide ra nge of commu n i t y

o rg a n i z a t io ns and pro g ra ms inc l ud i ng Head Start,

urban and rural community gro u p s, senior cent e r s,

a nd computer supplie r s. We will assess the results of

t he pilot projects and disseminate info r ma t ion about

p ro m i s i ng int e r v e nt io ns.

■ A re g io nal CIS of f ice is partne r i ng with a Canc e r

C e nt e r, a Head Start Cent e r, a group conc e r ne d

with urban polic y, and a group that supplie s

computers to children to develop techniques fo r

t e a c h i ng Head Start pare nts how to use computers and access health info r ma t ion on the We b. 

■ A no t her Cancer Center and re g io nal CIS of f ice are

p a r t ne r i ng to inc rease access to cancer info r mat ion and the use of technology by re s ide nts of an

e c o no m ically de p ressed area in the commu n i t y. 

■ A university and two re g io nal CIS of f ices are 

c o l l a b o ra t i ng to pro mote the use of, and tra i n i ng

by peer advocates fo r, a computer-based 

e duc a t ion pro g ram amo ng underserved wome n

d ia gnosed with breast cancer in a rural area in

o ne state and an urban area in ano t he r. The pro ject is he l p i ng some 280 African Ame r ican wome n

in the urban area play a larger role in their own

c a re by pro v id i ng them with access to online

i n fo r ma t ion. They are being tra i ned in the use of

laptop computers and are learning to get canc e r

i n fo r ma t ion and support over the World Wide We b.

T hese patie nts say it helps them connect with

people and info r ma t ion at all hours of the da y

a nd nig ht, especially when they are worrie d.

■ A collabora t ion between a university and a

re g io nal of f ice of the CIS is exa m i n i ng the use of

a low-literacy cancer info r ma t ion computer 

p ro g ram to de t e r m i ne its potent ial to inc re a s e

t he use of new commu n ic a t ion techno l o g ies fo r

health info r ma t ion by older adults in a group of

s e n ior cent e r s.

(For mo re info r ma t ion, go to

c a nc e rc o nt ro l . c a nc e r. go v / e o c c / dd p p . ht m l . )
90 The Nation’s Investment in Cancer Research

in their communities and addressing inequities in the

quality of and access to cancer care. The kit will contain instructional materials and examples of proven

strategies for effective cancer communications.

We are working to improve the quality and volume of communications related to clinical trials.

Research is underway to improve and assess the communication of risks, benefits, and other essential elements of the informed consent and decision making

processes. A Web-based educational program is

assisting research teams with issues related to the protection of human participants in research

( c m e . n c i . n i h . g o v, ohsr. od.nih.gov/cbt). And our new

Cancer Clinical Trials Education Series provides clinical trials information to the public, healthcare professionals, and patient groups. 

NCI has taken several steps for a c c e l e r a t i n g

research and development of interventions. We

solicited applications for grants to create up to five

Centers of Excellence in Cancer Communications

90 The Nation’s Investment in Cancer Research

THE PLAN — CANCER COMMUNICATIONS

Goal

Increase knowledge about, tools for, access to, and use of cancer communications by the 

public, consumers, patients, survivors, and health professionals – with a special focus on

diverse populations – to accelerate reductions in the U.S. cancer burden.

Objectives and Milestones for Fiscal Year 2003

1. Establish new data collection and analysis strategies to support cancer communications

planning and evaluation.

■ Analyze data from the Health Information National Trends Survey (HINTS) and make results

available to researchers and program planners as early as possible. $1.00 M

■ Explore the use of Internet-based data collection to follow a subset of people interviewed as

part of HINTS. $0.50 M

■ Conduct a HINTS survey of cancer survivors in parallel with the HINTS public survey to 

collect data on survivors’ use of different media, their risk perceptions, cancer-related behaviors,

personal cancer experiences, and use of complementary and alternative medicine. $1.50 M

■ Explore the need for national data collection about health professionals’ communication practices. $0.35 M

■ Continue to operate the NewMediacy listserv and health and lifestyle database to inform NCI’s

planning and evaluation efforts about which audiences use which new media and how they use

them. $0.20 M

■ Create a searchable database of cancer-related communication research reports accessible to

researchers and program planners. $0.50 M

2. Increase access to and use of cancer communications by all populations, especially

underserved populations. 

■ Analyze and disseminate the results of four Digital Divide Pilot Projects to test strategies to

increase access to and use of online and other interactive cancer communications by underserved populations. $0.50 M

■ Fund additional Digital Divide Pilot Projects and evaluate outcomes. $1.00 M

■ Transform the clinical trials Web portal to enable visitors to more quickly find information 

and resources. $1.00 M

$4.1 M

$2.5 M
R e s e a r c h in Fiscal Year 2002. The response was

excellent, showing that this initiative meets a real

need in the research community. The Centers will

encourage focused interdisciplinary studies to accelerate scientific developments in cancer communications, increase the number of investigators from a

range of disciplines who focus on the study of cancer

communications, and train investigators to conduct

cutting-edge communications research directly relevant to the context of cancer prevention, detection,

treatment, control, and survivorship (cancercont r o l . c a n c e r. g o v / c o m m u n i c a t i o n c e n t e r s ) .

NCI also supported a Community Clinical

Oncology Program based project to collect data from

newly diagnosed cancer patients to learn more about

their special communication needs . This information will be used for program planning and to assess

the need for additional research.

Through the use of technology and in response to

various needs, we are improving existing communicaExtraordinary Opportunities 91

3. Accelerate the pace of research and development of interventions in cancer 

communications. 

■ Continue to support Centers of Excellence in Cancer Communications Research. 

■ Establish interdisciplinary training partnerships and fund health communications laboratories

to develop and conduct training programs for researchers in growing areas, including risk communications and interactive health communications. $1.5 M 

4. Develop a menu of communication choices to meet the needs of all users, and especially

to increase knowledge about, tools for, access to, and use of these choices by diverse

populations. 

■ Develop new tools and products to facilitate cancer communications for the public, patients

and their caregivers, underserved populations, advocacy groups, health professionals, and cancer communicators. $2.00 M

■ Continue work with the Agency for Healthcare Research and Quality to fund research on

decision aids (“Making Quality Count for Consumers and Patients”). Link with Digital Divide

Pilot Projects to promote dissemination and use of interactive communication tools and collect

information on current levels of, and barriers to, use. $2.00 M

■ Assess the status of low-literacy research and national initiatives in order to develop a strategic

plan for low-literacy programs and materials. $1.00 M

■ Develop and promote a media toolkit to facilitate the media’s use of NCI’s resources in preparing cancer-related stories. $0.50 M

5. Improve the science of dissemination and the dissemination of science to assure that our

citizens realize the benefits of research investments.

■ Fund dissemination and diffusion supplements to grantees with proven interventions ready for

dissemination. $4.00 M

Management and Support

To t a l

$1.5 M

$5.5 M

$4.0 M

$1.5 M

$19.1 M
92 The Nation’s Investment in Cancer Research

tion channels and developing new ones. N C I ’s

NewsCenter Web site, launched in May 2001, provides journalists with easy access to downloadable

photos, graphics, video clips, and audio clips; transcripts of interviews with NCI scientists; traditional

press releases and backgrounders; and customized

l i nks to other relevant NCI Web sites.

NCI also is using several new features on the 

Web including an instant messaging service to

answer cancer questions submitted online

( c a n c e r.gov/Livehelp/vp/vp_cq.html), a natural language search system, the online NCI Publications

Locator (cissecure.nci.nih.gov/ncipubs), and new

minimum standards for improved navigability, cons i s t e n c y, and usability (usability.gov). A new

Communication Technologies Research Center for

usability testing, technology evaluation and demonstration, and training provides the tools needed to

design evidence-based cancer information prod u c t s

and services, and a new Emerging Te c h n o l o g i e s

Unit searches out and applies new and evolving

t e c h n o l o g i e s to cancer communications. 

Several activities illustrate our commitment to

improving dissemination of NCI research results.

We are working to heighten researchers’ unders t a n d i n g about the needs of end users of research

p r oducts and to increase the usefulness of the products so they will benefit people. 

We have put in place several mechanisms to assist

scientists in the dissemination of research findings.

To increase the likelihood that citizens will benefit

from our investment in research, we are strengthening NCI’s partnerships with voluntary health organizations, HMOs, and community organizations and

are planning to fund in 2002 six to eight competitive

supplements to NCI grantees who have effective cancer control interventions ready for dissemination. We

are convening, in collaboration with private organizations and other Federal agencies, an interdisciplinary

group to develop recommendations for intervention

researchers and encourage new partnerships among

researchers, funders, and receiving organizations. As a

unique component of the Transdisciplinary To b a c c o

Use Research Center (TTURC) program, the Robert

Wo od Johnson Foundation, as a cosponsor, has funded hiring a specialist at each TTURC to facilitate

communication with the public, researchers, and the

media. (See page 86.) In partnership with the

Agency for Healthcare Research and Quality

(AHRQ), we have commissioned an evidence-based

review of effective strategies to facilitate dissemination of cancer-related interventions. We will communicate the results through the World Wide We b ,

print, and other channels. And, in partnership with

the Centers for Medicare and Medicaid Services, we

are helping to support a national demonstration to

test a new Medicare smoking cessation benefit for

older smokers, including dissemination of an evidence-based smoking cessation guide for smokers ages

50 and older and a guide for Spanish speaking

Medicare beneficiaries. 

R e s e a r ch on Ta rgeted and Ta i l o re d

Communications Highlights Successes 

A group of NCI-spons o red health commu n ic a t io ns

re s e a rc hers re c e ntly teamed up to pre p a re artic l e s

for a special issue of the Journal of Family and

Community Health. They reported on their effo r t s

to develop commu n ic a t io ns for special populat io ns, such as As ia ns, African Ame r ic a ns and

H i s p a n ic s, and to ind i v idualize cancer info r ma t io n .

One team showed that focus groups could be

conducted through the Internet and therefore

could include people who would not otherwise

participate. Another group tested the feasibility

of a tailored, interactive computerized cancer

pain program for patients. In pilot research, the

majority of patients said the computer programs

were easy, enjoyable, and informative tools.

The computer programs extend the reach of

health professionals and permit better reporting

of patients’ pain and tailored advice based on

each patient’s unique pain profile.
E

ach of the 1,268,000 Americans who will be

diagnosed with cancer this year will battle a

very specific, very personal disease. While the

hundred-plus distinct diseases we call “cancer” have

several essential attributes in common, each type of

cancer has its own unique characteristics that affect

how it arises, how it progresses, and how it can be

most effectively treated. And while we have learned

much that is broadly applicable to all types of cancer

through our core research programs and the initiatives of the Extraordinary Opportunities, we must be

equally alert to the specific tendencies and behaviors

of each cancer type. This is why NCI plans, promotes, and carries out an ambitious program of 

disease-specific re s e a rc h. 

NCI charts the course for its disease-specific efforts

primarily through advice from expert Progress Review

Groups (PRGs). The PRGs are panels of 20 to 30

prominent members of the scientific, medical, and

advocacy communities that assess the state of the science for a single type of cancer or a group of closely

related cancers and make recommendations for future

research. Over a nine-month period, each PRG identifies gaps in our understanding of the disease under

s t u d y, barriers to progress, and key research priorities.

The process culminates in the wide release of PRG

findings and priorities in a comprehensive report. All

PRG reports become road maps that guide NCI and

the scientific community in their efforts to make

progress against specific types of cancer. To date, six

PRG reports have been issued. Six more PRGs are in

progress or planned. (See schedule, page 97.) 

N C I ’s extensive slate of PRGs includes breast,

prostate, lung, and other common types of cancer as

well as less common diseases like pancreatic cancer,

multiple myeloma, and brain tumors. By addressing

these more unusual types of cancer through the

PRGs, NCI hopes to raise awareness of the scientific

opportunities afforded by each disease and to stimulate much-needed research. 

RESPONSE AND COMMUNICATION

T

he NCI responds rapidly and enthusiastically to

PRG recommendations. For each PRG, NCI staff: 

■ Form an internal working group of disease-specific

experts to spearhead the Institute’s response to the

recommendations, identify gaps in our understanding, and propose new programs and initiatives where needed.

■ Thoroughly analyze the recommendations to

determine the extent to which they are being

addressed — or could be addressed — through

existing programs or efforts.

■ Reconvene the PRG to discuss what we learn

through this analysis and to clarify what gaps

r e m a i n .

Disease Specific Research 93

Planning National Agendas for

Disease-Specific Research

When I entered the clinical trial, my doctor said to me, “You are not going to die right away.” This was a big

surprise! I felt so bad and had been told that I could expect to live only a few more months. I just assumed I

was at the end of the road. After several tries that failed, they finally found a treatment regimen that seems to

have turned my cancer around — at least for now. This kind of thing is very unusual for pancreatic cancer. 

I have been so blessed and want others to know that there is hope.

- CH R I S T I N E, C L I N I C A L T R I A L PAT I E N T
■ Develop strategies to implement the recommendations, particularly in gap areas.

■ Communicate our decisions to the scientific community and enlist their active participation in the

implementation process.

■ Ensure that effective mechanisms are in place to

implement decisions.

■ Follow up to ensure that the recommendations

continue to be addressed.

■ Report on our results.

To ensure that researcher and advocacy communities

are aware of NCI’s disease-specific priorities, NCI is

developing a comprehensive, systematic plan for disseminating and promoting the PRG reports. PRGrelated information is distributed at major medical

meetings, in journals and newsletters, and on the

World Wide Web. NCI has also partnered with several advocacy groups to promote the priorities identified by various PRGs.

Even with all these efforts in place, we recognize

that the ultimate success of the PRG process depends

on researchers’ ability and willingness to undertake

research projects in disease-specific areas of critical

need. NCI encourages the scientific community to

respond to its disease-specific priorities by treating

the PRG reports as broad Program Announcements

that indicate the most pressing needs and opportunities, and notifies the community about current funding opportunities that address the PRGs’ recommendations through its Cancer Research Initiatives We b

site (cri.cancer.gov). Grant applications that reference a PRG report receive special consideration in

t h e funding exceptions process. (For more on the

exceptions process, see page 21.) 

Consumer advocates also play a key role in the

PRGs and their follow-up. Advocates are involved

throughout the PRG process, serving as PRG members and keeping their communities informed about

the PRG and its recommendations and mobilizing

in support of PRG priorities. They may also help

raise awareness of the priorities among researchers

and clinicians. 

HIGHLIGHTS OF PRG

RECOMMEND ATIONS

B

ased on review and analysis of the recommendations of the first six PRGs, it is clear that many of

the recommendations are, or could potentially be,

addressed by programs that are already in place. In

some cases modification or supplementation of an

existing program is sufficient to get the research on

track. The PRGs have also pointed to obvious gaps

in NCI’s disease-specific programs. For example:

■ The Breast Cancer PRG noted that our lack of

understanding of the biology and developmental

94 The Nation’s Investment in Cancer Research

My doctor said I had multiple my e l oma, and I said, “What’s that?” When

she said it was cancer, I was stunned.

I had never even heard of this disease.

Multiple my e l o ma is a cancer of

blood plasma cells that grow out of

c o nt rol and form tumo r s, usually in

t he bone ma r ro w. These tumo r s

i nt e r f e re with the blood-fo r m i ng

f u nc t io ns of the ma r row and the

a b no r mal plasma cells cease pro duci ng infectio n - f ig ht i ng ant i b o d ie s.

Multiple my e l o ma is one of the

blood system cancers that are rising

in inc ide nce – new cases are

i nc re a s i ng by nearly one perc e nt per

y e a r. An estimated 14,400 ne w

cases will be dia g nosed in 2001.

D e a t hs from this disease also are

i nc re a s i ng, and the avera ge patie nt

survives only three years from dia gno s i s. Ty p ically a disease of the

e l de r l y, my e l o ma is now striking

people as young as their twent ie s

a nd thirtie s. Multiple my e l o ma was

o ne focus of NCI’s Leuke m ia ,

L y m p ho ma, and My e l o ma (LLM) PRG,

w hose report was released in Ma y

2001; the PRG group re c o m me nde d

a large case-cont rol study to investigate the etiology of the three dise a s e s, as well as the de v e l o p me nt of

an infra s t r uc t u re and me t ho do l o g ie s

to better unde r s t a nd the int e ra c t io n

a mo ng immu ne func t ion, infectio u s

a ge nt s, enviro n me ntal tox i ns, and

lifestyle factors that can lead to the

diseases’ de v e l o p me nt .

Multiple myeloma incidence is on the rise.
genetics of the normal breast was a significant barrier to progress against the disease. The NCI

responded by joining several other NIH Institutes

to release a Program Announcement (PA) seeking applications for research on normal breast

development, as well as on changes in the breast

throughout the development of early and

advanced cancer. This PA has generated eight

new research projects.

■ The Prostate Cancer PRG told us that the lack of

validated animal models of prostate cancer was

severely impeding progress. Since then, four separate research teams have begun work on mod e l s

of prostate cancer through NCI’s Mouse Models of

Human Cancers Consortium.

■ The Leukemia, Lymphoma, and Myeloma PRG

found that the infrastructure for developing new

treatments of hematologic malignancies, particularly those exploiting molecular targets, is inadequate. They called for the development of consortia that would bring together experts across

multiple disciplines and institutions to participate

in the rapid discovery and development of cancer

therapies. The ultimate goal of the program

would be to shorten drug development time of five

to ten years to about two years through an alliance

among academia, industry, government, and

patients. NCI is currently investigating ways to

create and support these novel consortia.

Disease-Specific Research 95

My father died from pancreatic cancer.

My brother and I wonder if w e ’ ve

inherited a high risk for this awful dise a s e. Are scientists working on w a ys

to prevent this cancer and find out

w h o ’s at risk? 

Pa nc rea t ic cancer is a partic u l a r l y

de v a s t a t i ng disease because it

s p reads quic k l y, seldom causes

clear symptoms until it is

a d v a nc e d, and is almost universally

fatal. In 2001, an estima t e d

29,200 new cases will be dia gno s e d, with most patie nts living six

mo nt hs or less after dia g no s i s.

S e v e re wasting and pain are tra g ic

h a l l marks of panc re a t ic canc e r.

R e c o g n i z i ng the urge nt need fo r

i m p roved de t e c t ion, tre a t me nt, and

symptom ma na ge me nt of this dise a s e, NCI convened a Pa nc re a t ic

C a ncer PRG in 2000. The PRG

s t ressed the need to better unde rs t a nd how the no r mal panc re a s

develops and func t io ns — an

e s s e nt ial fo u nda t ion for re s e a rch on

how panc re a t ic cancers arise and

t he enviro n me ntal and other fa ctors that may influence the i r

g rowth and spre a d.

Pa n c reatic cancer continues to affect thousands.

N ew drugs provide hope for pr o s t a t e

cancer patients with bone metastases.

W hen prostate cancer spre a d s, it often invades the

b o ne s, whe re it causes severe, de b i l i t a t i ng pain.

Ho w e v e r, several drugs curre ntly under study ma y

combat bone me t a s t a s e s, slowing the spread of the

c a ncer and impro v i ng the patie nt’s quality of life.

For exa m p l e, the class of drugs known as bispho sp ho nates has alre a dy been established as effective

a g a i nst breast cancer and multiple my e l o ma, but

t hese drugs have not been cons ide red partic u l a r l y

effective against prostate cancer — until no w.

C l o dro na t e, a bispho s p ho na t e, has shown activity

a g a i nst prostate cancer me t a s t a s i s, opening the

door for further stud ies involving mo re potent 

b i s p ho s p ho na t e s, or hig her doses of the drug. 

A second drug, At ra s e ntan, targets the pro t e i n

e ndo t helin-1, which pro motes cell growth in bone

a nd which is overactive in prostate cancer cells.

F i na l l y, a combina t ion of che mo t he rapy and a

b o ne - t a rgeted ra d ia t ion drug, stro ntium-89 

(Sr-89), may pro l o ng the lives of men with

p rostate cancer that has spread to the bone s. 

Sr-89 is a ra d ioactive substance used to re l ie v e

b o ne pain caused by me t a s t a t ic prostate canc e r.

W hen injected by vein, Sr-89 moves into bone s

a nd delivers ra d ia t ion directly to cancer that has

s p read the re. Metastasis was a key topic of 

i nt e rest for the Prostate Cancer PRG, whose 

report is fo u nd at

p l a n n i ng . c a nc e r. go v / P R G R e p o r t s / P P R G R e p o r t / t o c. ht m .
Furthermore, NCI is taking steps to address a number

of broad scientific needs noted by several PRGs, such

as the need for research training and the development of biomarkers of disease. For example:

■ NCI is currently expanding the S p e c i a l i z e d

Programs of Research Excellence (SPOREs)

program to cover a number of the cancers addressed

by the PRGs, including gynecologic cancers, brain

tumors, leukemia, lymphoma, and myeloma.

S P OREs are described in detail on page 26-28.

■ Several PRGs have recognized a need for the

identification of biomarkers of disease. The E a r l y

Detection Research Network (EDRN) is dedicated to meeting this need. Projects specifically

related to prostate, lung, and ovarian cancers are

among those well under way, with others planned.

For more on EDRN, see page 75.

■ Several PRGs discussed the importance of more

accurate diagnosis and staging of cancer. Research

conducted through the The Director’s

Challenge: Toward a Molecular Classification of

Tu m o r s will facilitate diagnosis at the molecular

level, enabling greater precision in diagnosis and

treatment. To date, the Director’s Challenge has

stimulated some 22 supported projects covering a

diverse array of cancers including breast, prostate,

lung, brain, ovary, colon, and leukemia and lymphoma. See page 75 for more information on the

D i r e c t o r ’s Challenge initiative.

96 The Nation’s Investment in Cancer Research

N ew imaging technology improves early

detection for lung cancer.

S p i ral CT is a pro m i s i ng new technique that can be

used to detect lung cancer at a very early stage,

b e fo re it has had a chance to spre a d. This technique uses X-rays to scan the ent i re chest quic k l y,

in 15 to 20 second s, du r i ng a single bre a t h - ho l d. 

It is safe — the amo u nt of ra d ia t ion du r i ng a 

s p i ral CT scan is about the same as that absorbed

du r i ng a ma m mo g ram — and simple. But will

de t e c t i ng these early tumors re duce the like l i ho o d

of dy i ng from lung cancer? The NCI is working to

f i nd out. The year-long Lung Scre e n i ng Study

(LSS), began in the fall of 2000 to gauge the feasibility of a large r, mo re definitive study down the

ro a d. Through the LSS, we will learn, first and

fo re most, whe t her smo kers will be willing to be

ra ndomized to receive some t h i ng other than a 

s p i ral CT scan in a comparative study. The LSS will

also pro v ide important info r ma t ion about the me dical follow-up of people who have the scans, as

well as the costs involved. The Lung PRG, who s e

report was released in August 2001, discussed the

t o p ic of scre e n i ng ex t e ns i v e l y, calling for the ra p id

e v a l ua t ion of spiral CT as a me a ns of de t e c t i ng

c a ncer early and ultimately re duc i ng de a t hs fro m

l u ng canc e r.

We have to carefully weigh the potential benefit of every brain tumor surg e r y, chemother a py, or radiation tr e a tment against the risk of mental and

functional damage. And with childr e n ,

we worry about future learning or

d evelopmental pr o b l e m s. 

Many cancers have one or mo re 

s u b t y p e s, but brain and cent ral 

nervous system (CNS) tumors are

ex t ra o rd i nary in this re g a rd — mo re

than 125 types are known to ex i s t ,

a nd their symptoms, aggre s s i v e ne s s,

t re a t me nt, and outcome vary gre a t l y.

B e c a use brain tumors affect the

o rgan that is the essence of the

“self,” surg ical appro a c hes fo r

t re a t i ng most other cancers —

re mo v i ng the tumor and a border of

no r mal tissue if not the ent i re

affected organ — often cannot be

used without da ma g i ng vital me nt a l

p rocesses or brain func t io ns.

Mo re o v e r, ma ny brain and CNS

t u mors are highly re s i s t a nt to 

ra d ia t ion and che mo t he ra p y. The

B rain Tu mor PRG convened by NCI

noted these special challenges in its

report, published in 2000, and

called for the de v e l o p me nt of no v e l

t re a t me nt age nts and appro a c he s,

i nc l ud i ng new che mo t he ra p ie s,

t re a t me nts that target the immu ne

system, ge ne the ra p y, ant ia ng io ge nesis age nt s, and viral age nt s. 

B rain tumors pose unique challenges for r e s e a rc h e r s and patients.
ASSESSING THE IMP ACT OF THE PRG s

I

t is too early to fully assess this, but the early signs

are encouraging. NCI has recently begun the critical task of assessing the impact of the PRG effort

within the research community. As part of a system

for evaluating the PRG process and outcomes, the

Institute will analyze changes in grant applications,

funding levels, and types of research funded that

occur after the completion of a PRG. Starting with

the Breast and Prostate PRGs, NCI will issue a status

report two to three years after each PRG, and the

groups will reconvene to discuss the status of the recommendations and NCI’s response and to consider

further action. This process will provide valuable

information and insight about our directions in disease-specific planning. 

While the process may be refined over time, it is

clear that the combined perspectives of PRG members, NCI staff, researchers, and cancer advocates will

continue to influence the future direction of both

broad-based and disease-specific research. By working together, we can ensure the most effective use of

resources focused on both needs and opportunities for

advances against all cancers.

Schedule of Completed and Planned Progress

Review Groups

Completed August 1988 B reast Canc e r

Completed August 1988 P rostate Canc e r

J u ne 1999-November 2000 C o l o rectal Canc e r

November 1999-February 2001 B rain Tu mo r s

F e b r uary 2000-May 2001 Pa nc re a t ic Canc e r

April 2000-August 2001 L e u ke m ia - L y m p ho ma -

My e l o ma

August 2000-November 2001 L u ng Canc e r

December 2000-February 2002 G y ne c o l o g ic Canc e r s

Ma rch 2001-May 2002 K id ne y / B l a dder Canc e r

J u ne 2001-August 2002 S t o ma c h /

E s o p h a geal Canc e r

September 2001-November 2002 Liver/Bile 

D uct Canc e r

December 2001-February 2003 Skin Canc e r s

Disease Specific Research 97

N ew initiatives aim to improve br e a s t

cancer tr e a t m e n t .

T he find i ngs of clinical trials in breast cancer over

t he last ten years have pro v ided phy s ic ia ns and

t heir patie nts with a wealth of new info r ma t ion to

g u ide their tre a t me nt cho ices – but at the same

t i me, have also complicated their de c i s ion ma k i ng .

To help oncologists and patie nts choose between

ra d ia t ion the ra p y, che mo t he ra p y, or ho r mo ne 

t he rapy to try to eliminate cancer cells left behind

after surge r y, NCI co-spons o red a cons e nsus 

c o n f e re nce at the end of 2000 to synt hesize the

i n fo r ma t ion from re c e nt re s e a rch and ma ke 

re c o m me nda t io ns for ro u t i ne cancer care. The

b reast cancer experts partic i p a t i ng in the confere nc e

p ro v ided advice on the factors that should guide

t he cho ice of adjuvant the ra p y, as these fo l l o w - u p

t re a t me nts are known, and ma de re c o m me nda t io ns

about which patie nts should cons ider ho r mo na l ,

c he mo t he ra p y, or ra d ia t ion the ra p y. In add i t io n ,

c o ns e nsus confere nce partic i p a nts also cons ide re d

t he side effects and quality of life ex p e r ie nced by

p a t ie nts unde rgo i ng the various fo r ms of adjuvant

t he rapy and pro m i s i ng new dire c t io ns for this

re s e a rch. In other re s e a rch, NCI is spons o r i ng

c l i n ical trials to compare the effects of re mo v i ng

only one or a few lymph no des du r i ng breast 

c a ncer surgery to the standa rd, mo re invasive 

p ra c t ice of re mo v i ng mo re lymph no de s. 

I’ve been treating children with leukemia for over

t h i rty years now. We ’ re actually able to cure the

majority of the children we see now, and that’s 

nothing short of a miracle, in my book. 

Still, there ’s a lot to be done — too many childre n

s u ffer needlessly during their illness, and too many

c h i l d ren suffer devastating aftere ffects of their

t reatment. And even today, far too many childre n

die. I think we’re making pro g ress, though. I look

f o rw a rd to the day when we have leukemia 

(and all cancers!) under control — and I think we

may even see it in my lifetime.

- DAV I D, O N C O L O G I S T
30 Years Later . . .

Alan S. Rabson, M.D., began his career at the

National Cancer Institute as a resident in pathological anatomy in 1955. After serving as Deputy Chief

for Laboratory Pathology and Division Chief for

Cancer Biology, Diagnosis, and Centers, he became

N C I ’s Deputy Director in 1995. Recently, he talked

about NCI’s accomplishments since the passage of

the National Cancer Act in 1971 and about the

future of cancer research and care. 

In 1971, when the National Cancer Act was

signed, the goal was to cure cancer within five

years. Thirty years later, we still haven’t cured

c a n c e r. Why is this?

Well, 30 years later we do cure more than half of

all cancers. For example, nearly half of all highgrade lymphomas are cured. The overwhelming

majority of all testicular cancers are cured. We’re curing more breast cancer and ovarian cancer now than

ever before, and most all of this has come about since

1971. 

We’re also much more attuned to the importance

of detecting cancer early and the possibilities for

preventing its development. For example, when the

National Cancer Act was signed, screening mammography was not standard medical practice as it is

t od a y. In addition to regular mammography, women

at high risk for breast cancer now have the option of

taking drugs, such as tamoxifen, that may prevent

the disease altogether. 

But also, our goal now is to stabilize patients so

that while they still may have cancer, they can have

the longest period possible of high quality life. The

treatments we’re developing now are making this

possible for more and more people. For instance,

treatment with the drug gemicitabine prolongs the

lives of people with pancreatic cancer, and it’s possible that new drugs we’re developing may prolong

these people’s lives further. And the development

of TaxolTM in the 90s greatly improved and revolutionized the treatment of ovarian cancer.

After the Act was passed, a group of experts was

convened to figure out how we should plan and

conduct cancer research. What impact did that

group have on how we do science today? 

We convened several large groups out at a retreat

facility in Virginia. We brought in around a hundred people at a time — all the top experts in cancer research in the world. We asked them, “If you

had infinite resources, what would you do?” It was a

wonderful experience, but many of the goals we

came up with depended on things we had no technology for. For example, we talked about genes, and

what we could do if we could sequence or clone

them. We had the right ideas, but we were waiting

for molecular biology to catch up. Now we can do

things we never dreamed possible.

What has been the most exciting thing that has

happened during your tenure at NCI? 

In my 46 years here, everything has been exciting! But if I had to choose one thing, it would be

the advances in molecular biology and genetics that

have changed the world of cancer research and

opened doors for so many new opportunities to

explore. As we’ve come to understand the molecular signatures of cancer cells, we can classify tumors

98 The Nation’s Investment in Cancer Research

Hope and Promise Are Becoming More Real

Dr. Alan Rabson has seen it unfold.
When the National Cancer Act was adopted in

1971, there was widespread hope that the additional

resources and responsibilities that it would bring to

the NCI would soon lead to a “magic bullet” cure

for cancer. Instead, as a result of research over the

last thirty years, we now know that cancer is a complex set of diseases, for which there is no single cure. 

An examination of what we have learned in the

major fields of cancer research shows how far we

have come and why implementing the plans

described in this document is essential for continuing the remarkable progress of the last three decades.

■ Cancer Biology – Scientists have learned that

cancer is a disease resulting from multiple genetic

changes and have identified numerous hereditary,

environmental, life style, and infectious agents

that initiate the genetic changes that lead to canc e r. NCI research initiatives related to the

Signatures of Cancer Cells and Genes and the

Environment focus further exploration into the

inner workings of cells and the processes that contribute to cancer development and progression.

■ Prevention and Control – We have come to recognize the roles of tobacco, diet, and exercise in

cancer development and have identified numerous environmental carcinogens. We also know

that some individuals are more susceptible to

these exposures than others. Better understanding the many causes of cancer has opened multiple avenues to prevention, including chemoprevention. Numerous evidence-based interventions have been employed to better control canc e r. Continued research on Genes and the

Environment, Tobacco and To b a c c o - R e l a t e d

Cancers, Molecular Targets, and Cancer

Communications will lead to further improvements in the future.

according to their genetic characteristics. And the

future promises to be even more exciting, as we discover new, targeted, and effective means of cancer

treatment and prevention. One of the best examples of this is the development of a new, targeted

treatment for chronic myelogenous leukemia and

potentially other forms of cancer. And breast cancer

patients whose tumors have certain molecular characteristics have benefited tremendously from the

i n t r oduction of HerceptinTM, another targeted treatment. In addition, public support for basic biomedical research has become much stronger, in large

part because of the growth of the advocacy commun i t y. We’ve also enjoyed tremendous political support, which is a reflection of the popular support.

What can we expect from cancer-related science in

the next 5-10 years, and what will it mean for

p a t i e n t s ?

More patients will be cured, but more than that,

more people will live with a stabilized disease.

Will we ever cure all cancers? No. But we will

learn to manage most of them and patients will be

able to maintain a high quality of life — just as

people with heart disease can live well for many

years after their diagnosis.

30 Years Later 99

H ow It All Comes T o g e t h e r
100 The Nation’s Investment in Cancer Research

■ Early Detection and Diagnosis – Thirty years

ago, cancer was often detected only when it was

so far advanced that it was next to impossible to

treat it effectively. Tod a y, physicians are armed

with a variety of non-invasive screening and

detection tools including mammography,

c o l o n o s c o p y, ultrasound, and CT imaging as well

as tests of body fluids or tissue such as the PSA

for prostate, HPV for cervical, and CA-125 for

ovarian cancer. In some cases, they also can use

genetic testing to determine predisposition to a

specific type of cancer. We will continue to

make progress in early detection and diagnosis

through research and development on the

Signatures of Cancer Cells and Cancer Imaging.

■ Tr e a t m e n t – Tod a y, treatment is more targeted

and less debilitating: physicians use image-guided surgery and radiation therapy and surgical

techniques such as lumpectomy instead of mast e c t o m y. And we are beginning to develop drugs

such as HerceptinTM for breast cancer and

GleevecTM for chronic myelogenous leukemia

that target the specific genetic characteristics of

c a n c e r. Many more promising treatments are on

the horizon based on the discoveries and

advances of the past 30 years. Our continued

efforts in Molecular Target research and development and acceleration of NCI’s National

Clinical Trials Program are critical to making

these treatments a reality. 

■ Surviving Cancer and End-of-Life I s s u e s – At

the time the National Cancer Act was passed,

many people did not survive cancer at all. Tod a y

in the U.S. there are over eight million cancer

survivors who need care and support to make the

most of their lives. For those who lose the struggle with cancer, we have learned much in the

last thirty years about easing their pain at the

end of life. We are committed to improving our

performance in addressing survivorship and endof-life issues through continued research on the

Quality of Cancer Care and initiatives in Cancer

C o m m u n i c a t i o n s .

Continuing progress in cancer research will depend

on our ability to maintain a research system that

allows the scientific community to apply new insights

and emerging technologies, pursue innovative ideas,

and facilitate collaboration among experts from a

range of scientific disciplines. Cross-cutting to all of

these are our NCI Challenge efforts for Enhancing

I n v e s t i g a t o r-Initiated Research; building Centers,

Networks, and Consortia; Studying Emerging Tr e n d s

in Cancer; Reducing Cancer-Related Health

Disparities; building and maintaining Informatics and

Information Flow systems; and preparing future cancer scientists through Cancer Research Training and

Career Development programs.

Go to cra.nci.nih.gov/2_accomplishments/index.htm

for more information on the National Cancer Act

and the past 100 years of advances against cancer.
A c k n o w l e d g m e n t s

Each year the Na t io nal Cancer Ins t i t u t e

calls upon countless people at NCI and in

re s e a rch, prof e s s io nal, and advocacy org a ni z a t io ns aro u nd the country to pro v ide the i r

i ns ig ht s, perspectives, and expertise to

help us develop The Nation’s Investment in

Cancer Research Plan and Budget Proposal.

We ex p ress our gra t i t ude to all who contributed to this effort for the Fiscal Ye a r

2003 Plan.

S e v e ral NCI staff deserve special re c o g n it ion for their cont r i b u t io ns to the de v e l o pme nt of this do c u me nt. Cherie Nichols,

D i rector of the Office of Scie nce Planning

a nd As s e s s me nt, served as overall advisor

for the project. Kathie Reed, Bra nch Chie f

for Scie nce Planning, pro v ided leade r s h i p

a nd guida nce for each step of the pro c e s s

f rom conc e p t ua l i z a t ion to pro duc t io n .

Kathy Gallagher, Jane Lockmuller, Ka t e

N a g y, Jennifer Sutton, and Anne Ta t e m

w o r ked tirelessly along s ide the Champio ns

f rom aro u nd the Institute to conc e p t ua l i z e,

w r i t e, and ens u re the accuracy of the ma t er ial. Several other staff in the Office of

S c ie nce Planning and As s e s s me nt played

s ig n i f ic a nt supporting roles inc l ud i ng

Buddy Clark, Marilyn Duncan, Ke v i n

C a l l a h a n, Jim Corrigan, Bernard Glassman,

D. J. Joya, and Anna Levy. John Hartinger

a nd Ngan Nguyen in the NCI Fina nc ia l

Ma na ge me nt Bra nch ens u red the int e g r i t y

a nd accuracy of the budget info r ma t io n

with dilige nce and de d ic a t ion. Pa u l

L a M a s t e r s in the Office of Commu n ic a t io ns

e ns u red the quality and time l i ness of 

do c u me nt print i ng .

E x t ra o r dinary Opportunity and NCI

Challenge Champions

NCI Director D r. Richard Klausner served as

E d i t o r - i n - C h ief with support from D r. Alan

R a b s o n a nd D r. Robert Wittes. The NCI staff

members listed below served as Champio ns

for the Extra o rd i nary Opportunity and NCI

C h a l l e nge are a s. 

E x t ra o rdinary Opportunity Champions

G e nes and the Enviro n me nt – 

D r. Robert Hiatt, Dr. Robert Hoover

C a ncer Ima g i ng – D r. Ellen Feigal, 

D r. Daniel Sullivan

D e f i n i ng the Sig na t u res of Cancer Cells –

D r. Robert Strausberg

Molecular Ta rgets of Pre v e nt ion and

Tre a t me nt – D r. Robert Wittes, 

D r. Edward Sausville, Dr. J. Carl Barrett

R e s e a rch on Tobacco and To b a c c o - R e l a t e d

C a ncers – D r. Robert Croyle, 

D r. Neil Caporaso, Dr. Scott Leischow

C a ncer Commu n ic a t io ns – D r. Barbara Rimer,

D r. Susan Sieber, Ms. Mary McCabe

NCI Challenge Champions

I n v e s t ig a t o r - I n i t iated Research – D r. Marvin

Kalt, Dr. Dinah Singer

C e nt e r s, Ne t w o r k s, and Cons o r t ia – D r. Ellen

Feigal, Dr. Brian Kimes

Na t io nal Clinical Tr ials Pro g ram – D r. Robert

W i t t e s, Dr. Michaele Christian

S t udy i ng Eme rg i ng Tre nds in Cancer – 

D r. Rachel Ballard-Barbash, Dr. Brenda

E d w a r d s

Q uality of Cancer Care – D r. Joseph

L i p s c o m b, Dr. Martin Brown

R e duc i ng Cancer-Related Health Disparitie s

– Dr. Robert Hiatt, Dr. Jon Ke r n e r, 

D r. Harold Freeman

I n fo r ma t ics and Info r ma t ion Flow – 

D r. Kenneth Buetow, Ms. MaryAnn Guerra

C a ncer Research Tra i n i ng and Care e r

D e v e l o p me nt – D r. Brian Kimes

In add i t ion to these Champio ns, D a n

G r a u m a n, Susan Greenhut, Jill Johnson,

Cheryl Marks, Tracy Thompson, S t a c e y

Va n d o r, a nd Paula Zeller ma de sig n i f ic a nt

c o nt r i b u t io ns to the cont e nt and accura c y

of this do c u me nt .

Fiscal Year 2003 Planning Committee

Members of this committee helped to

e ns u re that this do c u me nt clearly and

a c c u rately describes the exc i t e me nt and

p romise of NCI ‘s effo r t s, our needs and

p l a ns, and the vision for the future of our

re s e a rch pro g ra ms.

D r. Richard Klausner

D i re c t o r, NCI

D r. Alan Rabson

Deputy Dire c t o r, NCI

D r. Robert Wittes

Deputy Dire c t o r, Extra mu ral Scie nce and

D i re c t o r, Division of Cancer Tre a t me nt and

D ia g nosis 

D r. J. Carl Barrett

D i re c t o r, Center for Cancer Researc h

D r. Joseph Fraumeni

D i re c t o r, Division of Cancer Epide m io l o g y

a nd Gene t ic s

D r. Peter Greenwald

D i re c t o r, Division of Cancer Pre v e nt io n

M s. MaryAnn Guerra

D i re c t o r, Office of Ma na ge me nt

D r. Joseph Harfo r d

As s o c iate Dire c t o r, Special Pro j e c t s

M r. John Hartinger

As s o c iate Dire c t o r, Fina nc ial Ma na ge me nt

D r. Marvin Ka l t

D i re c t o r, Division of Extra mu ral Ac t i v i t ie s

D r. Suresh Mohla, Chair

E x t ra mu ral Advisory Board

M s. Cherie Nichols

D i re c t o r, Office of Scie nce Planning and

As s e s s me nt

D r. Barbara Rimer

D i re c t o r, Division of Cancer Cont rol and

Po p u l a t ion Scie nc e s

D r. Susan Sieber 

D i re c t o r, Office of Commu n ic a t io ns

D r. Dinah Singer

D i re c t o r, Division of Cancer Bio l o g y

M s. Susan Wa l d r o p

D i re c t o r, Office of Scie nce Opportunitie s

D r. Lee Helman, Chair

I nt ra mu ral Advisory Board

D r. Frederick Appelbaum, Co-Chair

B o a rd of Scie nt i f ic Ad v i s o r s

D r. Michael Kastan, Co-Chair 

D r. Craig Thompson, Co-Chair

B o a rd of Scie nt i f ic Couns e l o r s

M s. Paula Kim, Member

D i rector ‘s Cons u mer Liaison Gro u p

D r. Phillip Sharp, Chair

M s. Ellen Stovall, Member

Na t io nal Cancer Advisory Board
National Cancer Institute (NCI) cancer.gov

National Institutes of Health www.nih.gov

Department of Health and Human Services hhs.gov

By email cisocc@pop.nci.nih.gov

By Internet cancer.gov/publications

By phone 1-800-4-CANCER

By fax 1-301-330-7968

This document online plan.cancer.go v

Provides links to:

■ NCI Initiatives – Details of initiatives related to the Extraordinary

Opportunities including program links

■ NCI Research Resources – Over 100 research services and tools for

cancer researchers

■ Funding Opportunities – Research funding and training

opportunities available through NCI

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Physician Data Query (PDQ®) and CANCERLIT®

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investigators

■ NCI NewsCenter – Recent major press releases from NCI 

■ Specialized Programs of Research Excellence – Information about

NCI’s SPORE program

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cancer trends in the U.S. 

NCI Science Planning and Assessment planning.cancer.go v

Provides links to:

■ Cancer Research Portfolio – A comprehensive database of

NCI-supported research

■ Progress Review Group Reports – Reviews of NCI’s programs for 

specific cancer types

■ Research Initiatives by Type of Cancer – Current NCI initiatives, many

with funding opportunities

Cancer Research Training cancertraining.nci.nih.go v

Research training, career development, and educational 

opportunities available through the NCI

Cancer Centers cancer.gov/cancercenter s

Information on the Cancer Centers Program with links to NCI’s national

network of Cancer Centers 

SEER seer.cancer.go v

Cancer surveillance data for the United States from the NCI

Surveillance, Epidemiology, and End Results Program

NCI Science Behind the News newscenter.cancer.gov/sciencebehind

Straightforward tutorials of basic concepts in cancer and cancer

research

Cancer Information Service cis.nci.nih.go v

The latest, most accurate cancer information and LiveHelp, online

instant messaging service available Monday through Friday from 

9:00 a.m. to 4:30 p.m. Eastern Time

Patients

Call the Cancer Info r ma t ion Service (CIS) at 1 – 8 0 0 – 4 – C A N C E R

(1–800–422–6237) Mo nday through Friday from 9:00 a.m. to 4:30 p.m.

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S e nd an email to c a n c e r m a i l @ c i p s. n c i . n i h . g o v with the one - w o rd 

me s s a ge “Help” to receive a cont e nts list and orde r i ng ins t r uc t io ns fo r

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Call 1-800-345-3300 or email c a n c e r m a i l @ c i p s. n i c. n i h . g o v to re q u e s t

C a nc e r Net Search Services to obtain PDQ® and CANCERLIT® info r ma t io n .

Valuable World Wide Web Locations

Other Ways to Obtain Information

Ordering This Document

NIH Publication No. 02-4373 T903