The National Cancer Institute

The Nation’s

Investment in

Cancer Research

A Budget Proposal for 

Fiscal Year 2001

Prepared by the Director

National Cancer Institute 

National Institutes of Health
Cancer surveillance – identifying and tracking trends in our national

cancer burden, and monitoring the factors that influence these

changes – is a crucial underpinning of our efforts to prevent and control cancer. For

example, increased surveillance efforts can help us understand and address the

unequal burden of cancer experienced by certain racial and ethnic groups in America.

To learn about NCI’s plans for all areas of cancer surveillance research, see page 92.

Surveillance

Scientists have learned

that all cells – normal,

precancerous, and cancerous – have

unique molecular features, or 

“signatures.” Learn how we’re using 

this knowledge to revolutionize cancer

detection and diagnosis – page 51. 

Signatures

Using “molecular targets,” we may be able to design cancer treatments

that are “customized” for many patients, determine immediately

whether or not a particular treatment is working, and even decipher the mechanism of

action by which a drug works. See page 57 to find out what a “molecular target” is

and how they’re being used to transform cancer prevention and treatment.

Molecular 

Targets

“Functional imaging” allows us to monitor physiological processes (such

as blood flow, oxygen consumption, or glucose metabolism) and molecular activities as they take place in the body. Turn to page 45 to find out how NCI is

using new cancer imaging techniques to improve cancer detection, diagnosis, and

even treatment. 

Imaging

Progress in cancer research is more dependent than ever on 

the synergy of multidisciplinary teams of investigators and 

on government, academia, and industry collaborations. See page 79 to learn how 

NCI’s Centers, Networks, and Consortia are linking vital resources to address 

important questions about human cancer. 

Centers

Our current clinical trials infrastructure is insufficient to handle the

many exciting new drugs and drug combinations emerging from our

Nation’s laboratories. See page 84 to learn about NCI’s proposed National Clinical

Trials Program that will pave the way for us to translate new discoveries into 

treatments and prevention strategies for patients.

Clinical 

Trials

Too few talented scientists are choosing careers in clinical oncology

research, and those that do are experiencing increasing clinical and

administrative pressures that impede their ability to conduct needed research. 

To learn more about NCI’s plans to meet this challenge – and to attract much-needed

basic and population scientists to cancer research – turn to page 96.

Training

Every day, NCI’s 

nationwide programs for

supporting cancer research are yielding

new discoveries, new prevention and

treatment approaches, and greater hope

for people with cancer and those at 

risk – see page 12 for highlights of

recent progress.

Highlights 

of Progress

The late-20th 

century revolution 

in communications has had a profound

impact on how we convey important

information about cancer detection, 

prevention, treatment, and risk to cancer

patients and those at risk. Turn to 

page 69 to find out how.

Communications

Did you know that tobacco

use is directly responsible for

30 percent of all cancers, and 20 percent

of deaths overall, in the United States?

See page 62 to learn about the NCI’s

planned program of basic and behavioral

research on tobacco and addiction.

Tobacco

How do our genes interact 

with environmental agents 

in the development of cancer? NCIsupported scientists are working to 

find out. See page 38.

Genes

In our country, 

some populations 

are more severely affected by cancer 

than others. NCI has an aggressive 

program of research, training opportunities, and organizational structures dedicated to understanding and addressing

the unequal burden of cancer in the

United States – see page 34.

Special 

Populations

NCI provides the Nation

with the most up-todate cancer information 24 hours a day, 

7 days a week – through the Internet,

and by phone, fax, and more than 600

print and audiovisual materials. Turn to

page 33 to learn the many ways you can

access NCI’s information services.

Information

Colorectal cancer kills

more than 50,000

Americans each year. Find out how 

NCI is fighting this disease – and 

the screening tests that are currently

available – page 22.

Colorectal

Cancer

In Brief
The National Cancer Institute

The Nation’s

Investment in

Cancer Research

A Budget Proposal for 

Fiscal Year 2001

The Nation’s Investment in Cancer Research, the Bypass Budget, communicates the needs and

plans of the National Cancer Institute, in accordance with the legislative mandate contained

within the National Cancer Act of 1971 [Public Law 92-218, Sec. 407 (b)(9)(A)]. This

request is provided directly to the President in the Fall of each year as he formulates his budget request to the Congress for the entire Federal government and more specifically for cancer

research. The amount exhibited within the President’s Budget may differ from the level

included in this document. The Congress, through the appropriations process, is empowered

to determine the final funding amount that is appropriated to the National Cancer Institute.

Prepared by the Director

National Cancer Institute 

National Institutes of Health
2 The Nation’s Investment in Cancer Research

Director’s 

Message

As we stand on the threshold of the 21st century, we can marvel at how far we’ve come

in the battle against cancer. A hundred –

even fifty – years ago, cancer was a poorly understood disease that killed the great majority of people who had it. Today, we are learning more each

day about how cancer arises from a single cell that

behaves abnormally, dividing uncontrollably and

leading, eventually, to the development of a

tumor. We also are learning about the ways that

genes, which direct the behavior of the cell, interact with a host of environmental agents to cause

cellular malfunction and disease. This basic

knowledge about the nature of cancer is providing

us with critical insights into how we can prevent

and detect cancer more effectively. And it is giving us the opportunity to improve treatment by

enabling us to design therapies that target the

machinery of the cancer cell. 

Thanks in large measure to the dedication and

hard work of scientists across the Nation, we are

making real progress against cancer. The rate of

new cancer cases has been declining and the cancer death rate falling. Powerful new technologies

are permitting us to detect and diagnose cancer at

an earlier stage, before it has had the chance to

spread. People with cancer are living longer, and

with a better quality of life, than ever before.

Truly, we are making progress, but for those

who are touched by this disease, we are not making progress quickly enough. The declining incidence means little to Marisol, a mother of three,

newly diagnosed with colon cancer, or to Paul, a

retiree whose golden years are darkened by

the specter of chronic lymphoma, or to the 

parents of sixteen-month-old Andrew, who is

fighting for his life against an aggressive neuroblastoma. The drop in the death rate is only an

abstraction to the Corelli family, who were prematurely robbed of a loving wife and mother by her

ovarian cancer, or to the classmates and friends of

Minh, a college student whose life was cut short

by leukemia. And although we have undoubtedly

made tremendous strides in our ability to detect,

diagnose, and identify people at risk for cancer, we

have much to learn about what people who find

themselves at increased risk should do. Just ask

Rachel, who at age 31 has learned that she has a

markedly increased risk of breast cancer due to an

altered BRCA1 gene, and now faces the agonizing

choice of what preventive measures, if any, she is

going to take to reduce her risk of this disease. 

Furthermore, other recent trends threaten to

overshadow our hard-won victories. The incidence

of melanoma, an aggressive skin cancer, has been

rising about three percent per year, although death

rates have remained constant, and incidence rates

for non-Hodgkin’s lymphoma continue, inexplicably, to rise. In addition, adolescents are now 

smoking and using tobacco products – a major risk

factor for lung and other cancers – at a troubling

rate, which may well reverse the currently falling

rates of lung cancer in coming years. Moreover,

certain racial and ethnic groups continue to be 

disproportionately burdened by cancer.

How, then, can we continue to build on our

recent accomplishments to make further muchneeded progress against cancer? First, we must 

sustain the proven research programs that have

enabled us to pursue a path of scientific excellence
and discovery in cancer research. At the National

Cancer Institute (NCI), we have created an infrastructure that promotes discovery, worked with

some of the most innovative and productive scientists in the Nation, and initiated ground-breaking

programs that have yielded critical knowledge,

improved patient care, saved lives, and improved

the quality of life for many cancer survivors. We

must continue to offer these programs our full

measure of support. 

At the same time, we cannot hesitate to seize

extraordinary opportunities to further the progress

brought about by our previous research successes.

Three years ago, we identified four areas of investment that, if exploited, could produce dramatic

progress against cancer. We have made tremendous strides in each of these areas, and our progress

is highlighted in this Bypass Budget, The Nation’s

Investment in Cancer Research: A Budget Proposal

for Fiscal Year 2001. In addition, we begin a new

cycle of progress by identifying three additional

areas of extraordinary scientific opportunity.

Finally, we must ensure that the full promise 

of our research findings is realized by translating

our findings rapidly from the laboratory into practical solutions that will benefit everyone. We outline how this will happen in the “Challenge” 

section of this document for, indeed, our greatest

challenge is to assure that the insights of science

become advances in medicine and public health.

This Bypass Budget outlines the progress we have

made in this critical area and defines our plans 

for the future.

This document describes the budget we believe

we will need to fund our research programs, as

well as the support we need to train the next generation of top-flight scientists. It also details our

activities in the crucial area of communicating 

up-to-date cancer information to patients, health

professionals, and people at risk for cancer. Finally,

it serves as our central planning document, laying

out clearly our funding priorities and presenting

our vision of the Institute’s direction. 

Since 1937, NCI has dedicated itself, through

its scientists and its resources, to the defeat of cancer. We have made tremendous advances, but we

cannot stop now. We must persevere in our work.

For all of the Minhs and Marisols and Rachels and

Pauls of the Nation and the world, we must persevere. Through the careful application of research

and discovery, the 21st century can and will be the

era in which cancer finally is conquered.

Richard D. Klausner, M.D.

Director

National Cancer Institute

Director’s Message 3
4 The Nation’s Investment in Cancer Research

Table of 

Contents

Director’s Message . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

2001 Bypass Budget Request . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Highlights of Progress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

Advances in Science and Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

Charting Our Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

Foundations for Future Discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17

The National Cancer Institute’s Role in Cancer Research . . . . . . . . . . . . . . . . . . .18

Planning and Priority Setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

Seeking Advice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

How We Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Supporting Our Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Extramural Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Support for Extramural Clinical Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Intramural Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30

Cancer Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

AIDS Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32

Training and Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32

Other Research Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

Extraordinary Opportunities for Investment . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36

Genes and the Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38

Cancer Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45

Defining the Signatures of Cancer Cells: Detection and Diagnosis . . . . . . . . . . . . . .51

Molecular Targets of Prevention and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . .57

Research on Tobacco and Tobacco-Related Cancers . . . . . . . . . . . . . . . . . . . . . . . . .62

Cancer Communications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69
NCI’s Challenge: Building the Capacity of the Future . . . . . . . . . . . . . . . . . . . . .74

Investigator-Initiated Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .75

Centers, Networks, and Consortia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79

National Clinical Trials Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .84

Informatics and Information Flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

Studying Emerging Trends in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92

Training, Education, and Career Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96

Features

The Consumer Advocate’s Role at NCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21

How We Spend Our Budget . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Understanding Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27

Informing Professionals and the Public: NCI’s Information Services . . . . . . . . . . . . .33

Selecting Extraordinary Opportunities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

The Path to a New Cancer Drug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56

Spotlights on Research 

NCI’s Intramural Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30

Addressing the Unequal Burden of Cancer – Special Populations Research . . . . . . .34

Malignant Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42

How Can Spiral CT Improve Early Detection of Lung Cancers? . . . . . . . . . . . . . . . .48

Viruses, Vinegar, and Vaccines – Preventing Cervical Cancer . . . . . . . . . . . . . . . . . .84

People’s Stories

Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .64

Table of Contents 5
6 The Nation’s Investment in Cancer Research

Executive 

Summary

T

he National Cancer Institute (NCI) leads

the Nation’s fight against cancer by supporting and conducting ground-breaking research

in cancer biology, causation, prevention, detection, treatment, and survivorship. Decades of work

by NCI-supported scientists have produced real

gains. The rate of new cancer cases declined an

average of nearly one percent each year between

1990 and 1996, while the cancer death rate fell,

on average, 0.6 percent per year during that same

period. Powerful new technologies are enabling us

to detect and diagnose more cancers at an earlier

stage, before they have had the chance to spread.

And many people with cancer are living longer,

and with a better quality of life.

Even so, cancer continues to be a major health

problem; for many Americans, it remains the most

feared of diseases. In addition, the burden of cancer falls disproportionately on certain racial, ethnic and socioeconomic groups. Although we have

made real and lasting progress against the disease,

it is critical that we continue to push forward

toward our ultimate goal – preventing and curing

all forms of cancer.

To more rapidly achieve our goal, NCI has

developed the following plan:

■ Sustain at full measure proven, productive

research programs.

■ Seize extraordinary scientific opportunities made

possible by our previous research discoveries.

■ Create and sustain mechanisms that build the

capacity to allow the scientific community to

apply rapidly evolving discoveries and emerging

technologies for the benefit of human health.

Sustain at full measure proven, 

productive research programs.

In support of the entire community of cancer

researchers, NCI has developed an infrastructure

of mechanisms, organizations, and networks that

link scientists, facilities, and information. Each

year, through NCI support, the efforts of thousands of scientists yield scientific advances in 

all of these areas. 

In addition to basic, population, and clinical

research, we support investment in new research

programs to address behavioral, surveillance, and

communications research, as well as studies on the

needs of cancer patients and survivors. We also

support cancer centers, community-based clinical

oncology programs, training opportunities, and

communications, education, and outreach programs for both health professionals and the public.

Seize extraordinary scientific 

opportunities made possible by 

our previous research discoveries.

In 1996, NCI began to systematically identify

areas in which focused efforts and increased

resources could help reduce the burden of cancer.

Through this effort, we selected four areas of

extraordinary opportunity for investment: Cancer

Genetics; Imaging Technologies; Defining the

Signatures of Cancer Cells; and Preclinical 

Models of Cancer. A plan of action addresses 

each of these opportunities. 

This year, as we prepared to launch our “second

generation” of efforts, we carefully evaluated our

direction and progress in each investment area. We

determined that the time is right to build on the

foundations we have laid over the past three years
Executive Summary 7

Summary

in each “opportunity area” to resolve

fundamental questions about cancer and

improve cancer detection, diagnosis,

and treatment. From this evaluation, we

also determined that we should broaden

our Cancer Genetics investment area to

include the complex ways in which

genes interplay with the environment

to affect cancer susceptibility and risk,

and integrate our efforts in Preclinical

Models into the other investment

opportunities. 

In this document, we identify three

additional areas of extraordinary opportunity: Molecular Targets of Prevention

and Treatment, Research on Tobacco

and Tobacco-Related Cancers, and

Cancer Communications. Each of these

areas holds exceptional promise for

advancing our knowledge of cancer and

for helping patients and those at risk.

Genes and the Environment

The new challenge in the study of cancer causation is to apply the emerging

tools of molecular genetics to understand how genes interact with an individual’s environment to cause cancer.

These studies will, as a rule, involve

large populations and will require new

types of research mechanisms and strategies for

interdisciplinary collaboration. Despite the complexities involved, this endeavor holds great promise in many ways: (1) Identifying cancer susceptibility genes with known pathways of action will

point to previously unsuspected carcinogens. 

(2) Studies of genetically susceptible groups will

make it easier to detect small variations in risk

posed by certain types of environmental exposures.

(3) Understanding how cancer susceptibility genes

interact with other genetic and environmental 

risk factors will result in new ways to diagnose,

All Sites

Female

Male

-3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0

Lung

Colon/Rectum

Breast (Female)

Prostate

Pancreas

Non-Hodgkin's 

Lymphoma

Leukemias

Stomach

Ovary

Brain & CNS

Annual Percent Change

Both

SEX

Annual Percent Change in U.S. Cancer Death Rates:

Top 10 Sites 1990-1996

By Sex, All Ages, All Races
prevent, and treat cancer. (4) Quantifying the

cancer risks associated with susceptibility genes

and environmental exposures will inform clinical

and public health strategies against cancer. 

Cancer Imaging

Over the last quarter century, refinements in imaging technology allow us to not only view structures anatomically, but to visualize physiological,

cellular, or molecular processes as they take place

in living cells of the body. Parallel developments

in image enhancement agents are improving our

ability to capture changes in the biochemical

makeup of cells and other living structures. But

despite our progress, we still have important work

to do before imaging technology can be applied to

its fullest potential – when it will enable physicians to precisely locate precancerous and cancerous lesions, biologically characterize a lesion to

predict how it is likely to respond to a specific

therapy, and directly monitor its response to 

treatment. 

Defining the Signatures of Cancer Cells:

Detection and Diagnosis 

All cells have unique, identifiable signatures –

specific characteristics such as genes that are

active and proteins and other products that the

cell manufactures. During the transformation of a

normal cell to a cancer cell, the signature changes,

signaling the presence of cancer. By identifying

and “reading” the signatures of cells, we can detect

and diagnose cancer early, before it has had a

chance to spread and while it may still be easily

curable. We also can use the information from a

cancer cell’s signature to choose the most effective

treatment, determine which cancers are likely to

spread, and gain important insights into the etiology of the disease.

Molecular Targets of Prevention and Treatment

Until recently, scientists working to discover effective prevention and treatment agents have faced a

formidable barrier: not knowing precisely what

cancer is. No longer is this the case. With the 

evolution of molecular biology and the emergence

of new technologies, we are gathering remarkable

knowledge about the nature of a cancer cell and

the molecular changes that occur during a tumor’s

development. The extraordinary opportunity

before us – to discover and exploit molecular targets for cancer prevention and treatment – arises

from the convergence of scientific advances in

several areas. A research emphasis on molecular

targets could lead to tremendous advances in prevention and treatment. Agents that target specific

characteristics of a cancer cell presumably would

leave normal cells alone and would be more effective and less toxic than most traditional

chemotherapies. By understanding the changes,

we can also develop targeted preventive drugs 

that can stop or even reverse those changes. 

Research on Tobacco and TobaccoRelated Cancers

Tobacco-related diseases are the most preventable

and costly cause of death in the Nation, claiming

450,000 lives each year. To respond to this ongoing crisis, we must comprehensively attack the

problem of tobacco use – expanding our understanding of tobacco addiction, increasing our

knowledge of biological mechanisms underlying

tobacco-induced cancers, designing targeted

approaches that prevent people of all ages from

using tobacco, developing ways to prevent the

onset of tobacco-related cancers in smokers and

former smokers, and developing treatments for

tobacco addiction and the cancers it causes. We

will take full advantage of the constellation of

recent scientific, public policy, social, educational,

and legal advances that are providing an unparalleled opportunity to address the tobacco problem

in ways that integrate biological and psychosocial

models of tobacco and addiction.

Cancer Communications 

Few health-related interventions have the potential of interactive health communications to

improve health outcomes, decrease costs, and

enhance consumer satisfaction. Indeed, effective

communication is central to cancer care, from 

primary prevention through survivorship. Today,

we are in the midst of a communications revolution. Experts are producing increasingly refined

approaches to health communications, and

changes in the role and accessibility of information are altering health care practices, patientphysician relationships, and the way consumers

8 The Nation’s Investment in Cancer Research
Executive Summary 9

Summary

acquire and use information. We need to refine

and apply these advances to improve outcomes in

cancer prevention, early detection, treatment, and

survivorship.

Create and sustain mechanisms that 

build the capacity to allow the scientific

community to apply rapidly evolving 

discoveries and emerging technologies

for the benefit of human health.

We are learning more each day about the basic

nature of cancer. Yet we are faced with the challenge of converting these findings into advances in

cancer detection, prevention, and treatment. If the

pace of discovery is like an eight-lane highway, our

current ability to translate those discoveries into

clinical application is like a country road. Where

the two meet, a bottleneck of good ideas occurs.

Our challenge is to expand the country road to an

eight-lane highway that moves discoveries swiftly

to their use in cancer care. Doing so means ensuring that sufficient technological resources, trained

scientists, and expanded infrastructures exist, and

providing the vision, creative environments, and

diverse resources needed to ensure there is no

delay between discovery and its application.

To respond to this challenge, we have identified

six key areas for investment: (1) InvestigatorInitiated Research; (2) Centers, Networks, and

Consortia; (3) National Clinical Trials Program;

(4) Informatics and Information Flow; 

(5) Studying Emerging Trends in Cancer; and 

(6) Training, Education, and Career Development.

Increased support in these areas will enable us to

strengthen our infrastructure and enable basic 

discovery to rapidly improve clinical practice. 

Investigator-Initiated Research

Investigator-initiated research – research proposed

and conducted by scientists in laboratories and

clinics across the country and here at NCI – is the

wellspring of scientific discovery. Discoveries made

through investigator-initiated research are critical

to reducing the cancer burden. We must create

mechanisms that link basic, clinical, and population-based researchers with state-of-the-art

resources and technologies, promote collaborations among researchers inside and outside of cancer research, and draw into cancer-related research

scientists from allied fields, such as chemistry, 

biology, physics, and mathematics. In addition, 

we must strive to expand our research portfolio 

to include a greater number of research proposals

that may be somewhat riskier or highly speculative, or that pursue novel paths. We also must

convert basic science discoveries into practical,

affordable, and effective ways of restoring cancer

patients to health and preventing cancer throughout our population.

Centers, Networks, and Consortia

We find increasingly that multidisciplinary teams

are needed to solve the “big problems” in cancer

research. It is necessary to create new kinds of

functional links among scientists in diverse disciplines. We also need to ensure that these

researchers have the tools and resources needed to

conduct these essential studies. For these reasons,

NCI must expand its Centers of Excellence and

NCI-designated Cancer Centers programs and

develop a variety of new research networks and

consortia.

National Clinical Trials Program

The research investment of the past decade has

brought about a dramatic increase in the number

of new therapeutic and preventive agents showing

enough promise to warrant testing in clinical trials.

However, our present clinical trials system is failing

to keep pace with these opportunities to improve

cancer care. While fewer than three percent of

patients with cancer participate in the clinical trials that define effective new prevention and treatment approaches, the number and complexity of

trials needed to determine the therapeutic roles of

the new generation of agents continues to grow.

Many more patient-volunteers are needed to help

establish the benefits of new agents and new combination treatments, and a sufficient infrastructure

to support these studies is needed.

Informatics and Information Flow

The power of computer-based communications

and the World Wide Web are making possible

unprecedented research opportunities. Paper-based

research systems are giving way rapidly to integrated systems that share information and knowledge

effortlessly and enable new discoveries to be made
TABLE 1

National Cancer Institute - 2001 Bypass Budget Request (dollars in thousands)

1999 2000 2001 2001 2001 Core,

Operating President’s Core Core and Investments 

Budget Budget Request Investments & Challenge

Request Request

Research Project Grants (RPGs):

Ongoing $983,129 $1,056,342 $1,166,993 $1,167,993 $1,172,793

New (New and Renewal) 377,516 353,517 366,244 500,132 673,212

Small Business Innovation Research 57,808 60,978 63,173 72,173 83,173

Subtotal (RPG’s) 1,418,453 1,470,837 1,596,410 1,737,298 1,929,239

Intramural Research 488,884 487,144 506,630 518,380 549,180

Cancer Centers 197,490 197,455 204,563 259,263 335,113

Clinical Trials Infrastructure:

Cooperative Clinical Research 126,205 125,460 129,977 149,477 249,827

Community Clinical Oncology 

Program (CCOPs) 52,161 54,312 56,267 61,767 111,967

Subtotal (Trials Infrastructure) 178,366 179,772 186,244 211,244 361,794

Training and Education 112,123 117,256 122,097 134,097 173,172

Research Support Contracts 275,087 298,569 309,519 399,680 490,165

Cancer Control Management 

and Support 89,882 82,640 85,946 94,946 97,246

Research Management and Support 108,965 110,065 114,468 129,468 148,468

Other 26,866 29,181 32,124 50,624 50,624

Total NCI $2,896,116 $2,972,919 $3,158,000 $3,538,000 $4,135,000

Cancer Control included above $301,259 $312,719 $334,278 $462,778 $565,578

at the researcher’s desk, not just in the lab. NCI

must construct a new information architecture 

for the cancer research process. This Cancer

Informatics Infrastructure will help speed the 

discovery process, translate the best discoveries

into clinical trials, and transform cancer care

through more effective and efficient information

exchanges. By drastically reducing the time and

effort required to make new discoveries or apply

existing discoveries, this revolution will result in a

dramatic acceleration of progress against cancer. 

Studying Emerging Trends in Cancer

Appropriate decision making in science and 

in public health depends on accurate, reliable

information about the incidence and impact of

disease. NCI uses data from the Surveillance,

Epidemiology, and End Results cancer registry 

program to identify and study trends, track the

impact of cancer on the general population, and

provide information to help researchers find out

why certain populations are affected by cancer

more severely than others. However, recent

changes in health care financing and delivery, the

revolution in informatics and computer programming technology, and the social and cultural

diversity of our country present new challenges

and opportunities in surveillance research. We

need to expand our data collection to include patterns of cancer care, as well as treatment and quality of life outcomes. In addition, new investments

are required to find tools that will improve the

10 The Nation’s Investment in Cancer Research
precision and expand the reach of cancer surveillance. NCI’s surveillance efforts should encompass

a broader spectrum of the racial, ethnic, socioeconomic, and cultural diversity of our country.

Greater efforts are needed to disseminate the

results of NCI’s surveillance research, and, finally,

we must create the training programs to prepare

the next generation of surveillance researchers. 

Training, Education, and Career Development

Currently, too few promising individuals are

choosing careers in cancer research. Those who do

are faced with a field of increasing complexity, yet

they have decreasing amounts of time reserved

from clinical and administrative responsibilities to

conduct important research, mentor new scientists, or obtain necessary continuing training for

themselves. New ways of educating, training, and

developing scientists are necessary to ensure that

technology advances are integrated rapidly into

the cancer research enterprise and that scientists

are prepared to work together in team settings to

unravel the complex factors contributing to

human cancer. 

To strengthen the infrastructure for discovery

that supports all of our research efforts, continue

progress in pursuing our Extraordinary

Opportunities for Investment, and speed the 

flow of discovery into application, the National

Cancer Institute requests the funding presented 

in Tables 1 and 2. 

Executive Summary 11

Summary

2000 President’s 2001 2001 2001 2001

Budget Core Investment Challenge Total

Research Project Grants $1,470,837 $125,573 $143,889 $188,940 $1,929,239

Intramural Research 487,144 19,486 11,750 30,800 549,180

Cancer Centers 197,455 7,108 54,700 75,850 335,113

Clinical Trials Infrastructure 179,772 6,472 25,000 150,550 361,794

Training and Education 117,256 4,841 12,000 39,075 173,172

Research Support Contracts 298,569 10,950 90,161 90,485 490,165

Cancer Control 

Management and Support 82,640 3,306 9,000 2,300 97,246

Research Management 

and Support 110,065 4,403 15,000 19,000 148,468

Other 29,181 2,943 18,500 50,624

Total $2,972,919 $185,081 $380,000 $ 597,000 $4,135,000

Challenge

14%

Investment

9%

Core

5% 2000

President’s

Budget

72%

TABLE 2

2000 Base Amount with 2001 Increases 

(dollars in thousands)
12 The Nation’s Investment in Cancer Research

Highlights of Progress

Scientific progress may sometimes seem to move

forward at a frustrating pace. Because advances

in basic research, prevention, and treatment are

incremental, it often takes years to see the cumulative effects of our efforts on populations at risk,

patient survival, and improved quality of life.

Moving from an insight to a tested, successful

intervention in people takes time, and there will

always be a lag between our investment in developing a solid knowledge base and the payoff for a

person with cancer or one at risk for the disease.

Yet every day, thanks to the dedicated efforts of

cancer researchers and clinicians, we are growing

closer to our goal of overcoming cancer. 

In these final years of the twentieth century, we

have seen an explosion of progress against cancer.

We have witnessed a number of important

advances culminating from many years of intensive effort. We have begun to gather significant

information from programs launched only two or

three years ago. And with our recent funding

increase, we have been able to launch innovative

new programs that will have far-reaching effects

into the next century. The following highlights 

of recent progress demonstrate how far we have

come against cancer, and offer a glimpse of what 

is to come as we continue to build on our successes to conquer cancer in a future that is no longer

so distant. 

ADVANCES IN SCIENCE AND

TECHNOLOGY

Preventing Cancer/Cancer Control

Finding effective ways to prevent cancer has 

long been a central focus for NCI and cancer

researchers. Prevention can take many forms, from

smoking cessation and other behavioral changes 

to vaccines or antimicrobial agents against cancercausing infections. Importantly, our increasing

knowledge of cancer biology is enabling us to

identify agents – both natural and man-made –

that may prevent cancer by interfering with the

biological processes underlying cancer development. In fact, more than 50 compounds currently

are being investigated for their potential efficacy

as cancer preventives. 

Closely related to cancer prevention, cancer

control encompasses research on the many diverse

aspects of translating proven technologies and

tested methodologies into routine practice in the

community. For example, cancer control research

may focus on identifying new ways to help people

stop smoking, or to encourage people to adopt a

healthier diet, or to communicate health risks to

certain population groups. NCI’s commitment to

ground-breaking cancer control research is 

evidenced by its new Extraordinary Opportunities

in Research on Tobacco and Tobacco-Related

Cancers (see page 62) and Cancer

Communications (see page 69).

■ In recent results from the Breast Cancer

Prevention Trial, tamoxifen, a drug long used

for breast cancer treatment, led to a 49 percent

reduction in the incidence of primary breast

cancer during the treatment period in women

at high risk for the disease. This outcome marks

an important landmark in this line of research.

However, because tamoxifen may have serious

long-term side effects, NCI recently began

recruiting volunteers to participate in a study

to determine whether the drug raloxifene is as

effective in reducing breast cancer risk as

tamoxifen, but with fewer undesirable side

effects. The Study of Tamoxifen and Raloxifene

(STAR) will compare the effectiveness and the

long-term safety of these two medications in

women at increased risk for breast cancer. 
Highlights of Progress 13

Highlights

■ Some women who are at high risk of breast

cancer make the difficult decision to have both

breasts surgically removed, a procedure known

as bilateral prophylactic mastectomy (PM). In

a recent retrospective study of 639 women with

a family history of breast cancer who had

undergone the procedure, PM was associated

with a 90 percent reduction in the incidence

of breast cancer. And in another study, prophylactic oophorectomy – surgical removal of

the ovaries – was found to reduce breast cancer risk by about 40 percent for women with

cancer-predisposing BRCA1 mutations.

■ The sale of cigars in the U.S. has been increasing since 1993, but until recently little was

known about their health effects. However,

researchers have found that compared with

nonsmokers, cigar smokers were at increased

risk of lung and upper aerodigestive tract 

cancer, as well as heart and lung disease. These

important findings highlight the need for 

prevention efforts aimed at cigar smokers. 

■ Because tobacco use is responsible for over 

30 percent of all cancers, research on more

effective smoking prevention and cessation

approaches is a cornerstone of the Institute’s

cancer control efforts. Two recent studies have

added to our knowledge. In one, researchers

found that the passage of a comprehensive

ordinance ensuring merchant compliance with

tobacco age-of-sale laws in seven communities

significantly reduced daily smoking among

eighth, ninth, and tenth graders, compared to

communities without such an ordinance. In the

other, women who participated in an exercise

program concurrently with a behavioral smoking cessation program had a higher success rate

than women who underwent the behavioral

program but did not exercise. In addition,

women in the exercise program had gained less

weight by the end of the program. 

Detecting Cancer

New technologies that will enable us to detect and

diagnose cancer early, before it has had the chance

to spread, are on the horizon. Imaging devices and

modalities are being developed and tested that

allow us to visualize the cell with greater precision

than ever before (see page 45). In addition, 

new methods of reading the signatures of cells 

(see page 51) are enabling us to identify the subtle

differences between normal and cancer cells, and

are leading us to the day when only a simple 

blood test is needed to detect cancer anywhere 

in the body. 

■ Current methods for the non-invasive detection of small tumors are limited in their ability

to distinguish small areas of abnormal cells from

larger surrounding areas of normal tissue.

Researchers have developed a new method to

more precisely image tumor cells. They injected

tumor-bearing mice with a unique imaging

agent composed of near-infrared fluorescence

imaging probes coupled with a novel copolymer

that moves efficiently into tumor cells. When

the agent was absorbed into the cancer cells,

enzymes within the cells “activated” the agent

and caused it to fluoresce. The fluorescence

could then be detected non-invasively. The

agent was not activated in non-tumor cells.

Using this technique, investigators were able to

image tumors smaller than three-tenths of a

millimeter in diameter. Although this technique is in the early stages of development, it

shows great promise for the detection of very

small tumors.
Treatment Advances

As recently as thirty years ago, when legislation

launched the National Cancer Program, the idea

of curing cancer seemed a remote ideal. This ideal

is now a reality for a growing number of cancers

and within our grasp for many others. Today, using

insights gleaned from discoveries about cancer

biology, we are learning to tailor treatments for a

specific cancer in a specific individual, to optimize

the effectiveness of traditional treatments, and to

target treatments to the cellular machinery of 

specific tumors. Our great hope is that targeted

treatments will prove to be more effective and 

less toxic than our current approaches.

■ An exciting approach to cancer treatment is

immunotherapy, or treatments in which the

patient’s own immune system is coaxed to recognize and eradicate cancer cells. One targeted

immunotherapeutic approach that recently has

met with exciting success involves the use of

monoclonal antibodies, proteins derived from

cells found in the body’s own immune system,

that attach to the surfaces of cancer cells and

deliver a deadly substance directly to them.

Based on clinical trial results, two monoclonal

antibodies recently have been approved for use

in cancer treatment: Rituxan® for B-cell lymphoma, and Herceptin® for metastatic breast

cancer. Clinical trials are underway to determine whether these agents may be used or

enhanced to combat other types of cancer.

Another type of immunotherapy involves 

cancer treatment vaccines. NCI is sponsoring

more than 70 vaccine therapy trials, including

studies on using vaccines to treat melanoma

and cancers of the breast, prostate, cervix, 

kidney, pancreas, and ovary.

■ Another evolving treatment approach targets

the process of angiogenesis. Presently, about 

20 angiogenesis inhibitors – agents that block

the development of tumor-nourishing new

blood vessels – are being tested in human trials,

and others showing promise in animal studies

will soon enter human trials. For example, the

drug thalidomide, long banned from medical

practice for causing severe birth defects in children born to mothers who took the drug during

pregnancy, has been shown to be a potent

angiogenesis inhibitor. In a small trial of

prostate cancer patients, thalidomide caused a

decline in the biomarker PSA in 68 percent of

the patients – an indicator that thalidomide

could be effective against prostate cancer. In a

separate study, thalidomide was shown to induce

tumor shrinkage in 45 to 50 percent of

patients with AIDS-related Kaposi’s sarcoma.

■ Our success in treating childhood cancers, 

particularly leukemia, was the first proof that

cancer could be treated and cured. Years of 

trials focused on improving chemotherapies for

children with acute lymphocytic leukemia

(ALL) resulted in our current ability to cure 

75 to 80 percent of children diagnosed with

this disease. For 20 percent of children with

ALL, however, our treatments were ineffective

and the children fared poorly. Results of a new

trial using a modified chemotherapy regimen

have shown a 70 percent drop in the rate of

treatment failure in these high-risk children.

■ Five clinical trials involving women with locally and regionally advanced cervical cancer

showed that when cisplatin-based chemotherapy was given concurrently with radiation therapy, the risk of cervical cancer death was

reduced by 30 percent. Based on these definitive results, NCI strongly urges that physicians

consider adding chemotherapy to the treatment

of women who require radiation therapy for

cervical cancer.

■ Results from clinical trials under the long-running National Surgical Breast and Bowel

Project show that adding tamoxifen to lumpectomy and radiotherapy in women with ductal

carcinoma in situ (DCIS) reduces the risk of

subsequent invasive breast cancer. Taken

together with results of an earlier trial, these

findings suggest that lumpectomy, breast irradiation, and tamoxifen can safely substitute

for mastectomy in the treatment of DCIS. In

addition, women with DCIS treated with

lumpectomy alone have a significantly

increased risk of eventually developing breast

cancer, and thus should be considered a high14 The Nation’s Investment in Cancer Research
risk group that merits consideration for preventive treatment with tamoxifen.

■ 3-Dimensional Conformal Radiation Therapy

(3DCRT) is a new approach that employs

sophisticated computer technology to fit the

treatment field more tightly to the tumor, in

three dimensions, than was possible using conventional techniques. Researchers used 3DCRT

to treat patients with advanced prostate cancer

and found that they could safely give higher

doses of radiation to the tumor and increase

the probability of local tumor control. Using

an advanced form of 3DCRT, IntensityModulated Radiotherapy, significantly

decreased treatment complications among 

the same group of men.

Understanding Cancer and its Causes

With the knowledge that cancer is a genetic 

disease, we now look to our genes for clues about

how the disease develops and progresses in the

body. As a first step in this search, we are working

to identify the mutated genes that give rise to cancer. A second – and equally important – step is to

determine how these genetic changes contribute

to cancer. 

■ Newly developed technologies now enable us 

to develop mouse models of human cancers by

altering or inactivating mouse genes and introducing into mice the same mutations that occur

in humans. Using such models, cancer

researchers recently identified a gene, Smad3,

that plays a role in the development of colorectal tumors. Researchers also elucidated the role

of the normally functioning PTEN gene, whose

mutated form is found in a large percentage of

prostate, brain, breast, endometrial, skin, and

kidney tumors. These discoveries will pave the

way for further study of the biological changes

that underlie cancer, and may even lead to new

preventive or treatment interventions. 

■ As noted above, a number of angiogenesis

inhibitors are now being tested in clinical trials.

This is a result of our successful efforts to

untangle the mysteries of cancer biology, and

the subsequent growth of our understanding of

angiogenesis. The prevailing view holds that

most tumors originate without blood vessels,

and only induce angiogenesis once they grow to

a specific size. Important new evidence suggests,

however, that some tumors initially coopt existing vessels to form a well-vascularized tumor,

but the coopted vessels quickly regress and the

tumor loses many of its cells. Ultimately, the

remaining cells are rescued by angiogenesis –

through the collaboration of the angiopoietin-2

(Ang-2) and vascular endothelial growth factor

(VEGF) proteins – and the tumor continues to

grow. These findings suggest that inhibiting

VEGF, a powerful angiogenesis stimulator, can

impede tumor growth by preventing this

process and perhaps promoting the regression of

fragile new tumor vessels. And Ang-2, apparently the earliest marker of blood vessels disturbed by tumor cells, may prove useful for early

detection and as a treatment target.

■ Newly developed tools are helping scientists

perform large-scale analyses of the vast human

genome to genetically characterize tumors,

information that can help to explain why

patients diagnosed with the same cancer differ

dramatically in their responses to treatment,

and in their prognoses. For example, the

Lymphochip, a computer chip-like device with

DNA from more than 15,000 genes important

to both the immune system and lymphoid cancers, is enabling researchers to study the genes

active in non-Hodgkin’s lymphoma, a cancer

rising in incidence. The lymphochip promises

to be a useful tool for detecting lymphomas

early, analyzing risk, and selecting targeted

treatments. A similar device, an affinity-based

biochip, was developed by NCI and FDA investigators to generate biomarker profiles of 

normal, precancerous, cancer, and metastatic

cells from esophageal, prostate, colon, and

liver tissues. Biomarker pattern profiles reveal

changes in protein expression as tissue cells

transition from normal, to premalignant, to

invasive cancer; this new technology could be

extremely useful in the discovery of diseaseHighlights of Progress 15

Highlights
related proteins, therapeutic assessment, and

treatment toxicity monitoring.

■ Our research on cancer also has revealed that

elements in our environment play a significant

role in cancer’s development. Tobacco use, for

example, accounts for about one third of cancer

deaths in this country. Recently, several groups

of scientists found intriguing evidence of a 

possible genetic predisposition for smoking,

accounting for some peoples’ inclination to

smoke or inability to stop. Greater knowledge

of how these genes influence smoking promises

to provide important clues about how some

people become addicted to nicotine, and how

we can effectively help smokers stop smoking.

CHARTING OUR FUTURE

NCI’s mission to conquer cancer – to reduce and

finally remove the burden of this disease on present and future generations – is the driving force

behind the Institute’s diverse research programs

and activities. Planning for a future free from the

fear of cancer requires that we leverage the value

of our growing body of knowledge about cancer,

and that we challenge the research community to

go beyond its customary practices to achieve our

ultimate objective. We must develop initiatives,

programs, and new partnerships to most effectively

use new discoveries, exploit scientific opportunities, and apply emerging technologies to prevent,

detect, treat, and control cancer. 

NCI has spent much time and effort developing

and supporting an infrastructure that sustains the

research programs that today are enabling us to

pursue a path of scientific excellence and discovery

in cancer research. In tandem, we have established

a tradition of seeking better ways to inform the

process of identifying needs and opportunities in

the cancer field, setting priorities, and implementing decisions and recommendations that lead to

new or improved research initiatives and programs.

■ NCI recently assembled Progress Review

Groups composed of researchers, health professionals, industry representatives, and lay advocates to assess the state of our knowledge, identify scientific opportunity and need, and chart a

course for future study in two high priority

research areas: prostate cancer and breast cancer. NCI now is using the Groups’ recommendations to help set a national research agenda

in these areas. A colorectal cancer PRG is

planned for this year. 

■ Working Groups and Implementation Groups

also play a critical role in charting the course 

of research. For example, one such group, the

Tobacco Research Implementation Group

(TRIG), was charged with establishing NCI’s

tobacco-related cancer research priorities for

the next five to seven years. Another group,

the Surveillance Implementation Group

(SIG), was charged with identifying priority

cancer surveillance research areas and optimal

strategies for using surveillance measures to

advance our knowledge of cancer. 

■ NCI also has engaged groups of experts outside

the Institute to perform in-depth evaluations 

of various programs within the Institute

and recommend ways to enhance the structure

and function of the programs under study. 

For example, a recent review of the

Developmental Therapeutics Program (DTP),

NCI’s organizational focal point for new cancer

treatment development, highlighted the need

for DTP to respond to the needs of rapidly

changing science and technology. The review

group emphasized that new basic knowledge

and technologies must be integrated into the

process of discovering and developing anti-cancer drugs to allow DTP to meet the challenge

of drug development in the next decade. In

addition, recommendations from a review of

the clinical trials program resulted in a recently launched restructuring of our treatment clinical trials program. In this first major system

reform in forty years, we hope to ensure the

best science, improve physician and patient

access to trials, and enhance program efficiency

and effectiveness.

16 The Nation’s Investment in Cancer Research
FOUNDATIONS FOR FUTURE

DISCOVERY

To conquer cancer, NCI must not only pursue new

knowledge, but ensure that we have the trained

scientists, the technologies, and the necessary

infrastructures poised to take our considerable

knowledge about cancer and apply it to reduce the

burden of suffering it causes. These are the foundations for discovery that support our continued

successes, and they must be continually evaluated,

strengthened, and expanded to enable us to fully

seize opportunities for progress. Important components of our foundations for discovery were

launched or enhanced this year.

■ The Cancer Genome Anatomy Project

(CGAP) was established by NCI two years ago

to systematically identify the gene expression

patterns that characterize human cancer. We

have made important progress in this project.

For example, we have catalogued approximately

70,000 genes that are expressed in cancers and

their precursors; of these, about 30,000 are 

previously unknown genes. 

■ Through the Director’s Challenge: Toward a

Molecular Classification of Tumors, NCI is

challenging the scientific community to pursue

research harnessing the power of molecular

analysis to create a system for classifying tumors

according to their molecular profiles. This

“Director’s Challenge” is intended to lay the

groundwork, over a five year period, for changing our tumor classification system from one

based on visual characteristics to one based on

molecular characteristics. This information will

fundamentally change our approach to diagnosing cancer, to choosing cancer therapy, and to

predicting a patient’s outcome. 

■ Over the past two years, CGAP also has

enabled the discovery of hundreds of potential

markers for cancer, bringing us closer to the

possibility of sensitive, accurate, and predictive

tests for early cancer detection. With new funds

received this year, the Institute has established

the Early Detection Research Network

(EDRN), a national scientific consortium of

academic and industrial researchers who will

work toward rapidly developing and testing

such markers for cancer. Ultimately, this

research is expected to yield simple tests for

detecting all types of cancers that can be 

performed on easily sampled body fluids.

■ To ensure that we not only fill but expand the

pipeline to new cancer prevention and treatment approaches, NCI recently initiated the

Rapid Access to Intervention Development

(RAID) program. Through this program, we

will be able to identify promising proposals and

fund the rapid movement of new therapeutic

reagents from the laboratory to the clinic.

Because of its initial success, we have decided

to expand RAID and to launch RAPID, a 

program offering the same process for potential

preventive agents. 

■ Americans increasingly are turning to complementary and alternative medicine (CAM) for

treatment and supportive care of numerous 

diseases and conditions, including cancer. In

response to this growing trend, NCI has established the Office of Cancer Complementary

and Alternative Medicine, which seeks to promote and support research in the various disciplines and modalities associated with CAM as

they relate to cancer diagnosis, prevention, and

treatment and the management of cancer

patients. 

■ Because cancer strikes certain racial and ethnic

minority groups disproportionately, NCI recently launched the Special Populations Networks

for Cancer Awareness Research and Training.

The Networks will fund a diverse group of

research projects aimed at improving cancer

prevention and control in minority and underserved communities. Principal goals of the new

Networks will be to develop and maintain partnerships between scientific researchers and

community leaders in an expanded range of

minority and underserved populations, develop

and test community cancer awareness activities,

support minority enrollment in clinical trials,

and encourage minority scientists to participate

in cancer research. Initial awards under the 

program will be made in March 2000.

Highlights of Progress 17

Highlights
18 The Nation’s Investment in Cancer Research

The National Cancer Institute’s 

Role in Cancer Research

T

he National Cancer Institute (NCI) is

charged to lead our Nation’s research effort

to conquer this disease in all its forms. As

the Federal focal point for cancer research in this

country, NCI conducts, coordinates, and funds

cancer research, and provides vision and leadership for the cancer research community. Each day,

across the United States and around the world,

thousands of NCI-funded researchers and clinicians are joined together by a common goal – they

are working toward a day when cancers are an

uncommon and easily treatable set of diseases. 

NCI supports this vital work through research

programs that seek answers to the many remaining

questions about how best to prevent and treat cancer. Pursuing these answers can take one of two

interrelated and complementary paths – studying

the cancer cell itself to uncover biological processes

broadly applicable to all cancers, or studying one

of the more than 100 specific types of cancer.

Though these research approaches appear to be

divergent, they are inextricably linked, and in

fact, most fruitful when there is extensive interplay and cross-fertilization between them. As we

develop an understanding of biological processes

common to many tumor types, we gain new

knowledge that can be applied to cancer-specific

research, and as we make discoveries about a specific cancer, new questions about themes common

to all cancers are prompted.

Research on common biological processes,

broadly applicable research, focuses on uncovering

features that are common to all normal, precancerous, and cancerous cells. Basic research has

taught us that one or more cellular mechanisms –

cell growth, cell death, invasion, metastasis, avoidance of immune system attacks, and the accumulation of genetic changes that lead to cancer – are,

in different combinations, responsible for most

cancers. In addition to providing us with new

insights into mechanisms common to cancer cells,

basic research helps us to better distinguish one

cancer from another based on molecular characteristics. Distinguishing cancers according to their

molecular characteristics is becoming as important

as the traditional way of defining a cancer by the

site in which it arose. 

Basic research is not abstract; rather, it is the

generation of essential knowledge that can be

applied directly to each specific type of cancer

that people experience. For example, scientists

studying the process of angiogenesis, the formation

of new blood vessels that tumor cells exploit to

gain nutrients and growth factors, identified several potential anti-angiogenesis agents. The discovery of these agents, which may prove effective in

combating a variety of human cancers, might not

have occurred without broad research into the

basic biological processes common to all cancers.

Disease-specific research is aimed at uncovering

the biological characteristics that are unique to

each specific cancer, such as breast or prostate

cancer. Here the goals are to design effective

methods of preventing, detecting, diagnosing, and

treating the cancer, and to address disease-specific

survivorship issues. Disease-specific research also

yields information that applies to many diverse

cancers. For example, researchers studying the

very rare childhood cancer of the eye called

retinoblastoma discovered a gene, Rb, that when

altered is the trigger that leads to retinoblastoma

development. Scientists continued to study Rb and

discovered the interconnected molecular machinery of a cellular circuit called the Rb pathway. 
This pathway is found in all cells, not just those

that give rise to retinoblastoma, and at least one

component of the Rb pathway is altered in every

human cancer. Thus, a discovery unique to

retinoblastoma eventually led to an understanding

of a pathway that is found in all cells.

Our efforts to answer the key questions of cancer research through either broadly applicable

research or disease-specific research involves four

classes of investigation – laboratory, clinical, population, and translational. Laboratory research

focuses on the biology of cancer, the fundamental properties of cancer-causing

agents and processes, and the body’s

defense against and response to cancer. In

the clinic, research is carried out on cancer prevention, diagnosis, treatment, and

rehabilitation. Population research focuses

on the causes, risks, predisposition, incidence, and behavioral aspects of cancer.

Finally, translational research builds

bridges and intersections between and

among the classes of research. It facilitates

the movement of discoveries from laboratory and population research into the clinic and,

conversely, provides a way for clinical insights to

help direct laboratory and population-based

research. This flow of information among the laboratory, the clinic, and the community helps to

drive research in new directions.

How do we know what questions to pursue in

these four classes of research, be they broadly

applicable or disease-specific? The keys to establishing this scientific direction are our planning

and priority-setting processes; program review,

progress review, and implementation efforts; and

input we receive from our advisory groups and the

community. 

PLANNING AND PRIORITY SETTING

Planning – identifying needs and opportunities, setting priorities, implementing decisions and recommendations, and making sure that a reliable infrastructure supports all of our initiatives – is an integral part of all NCI activities. Setting NCI’s funding

priorities is a complex and dynamic process driven

by several principles. We must support the

full range of research activities necessary to

conquer cancer; therefore, we strive for a

balanced portfolio of research in behavior,

epidemiology, control, prevention, detection, diagnosis, and treatment, as well as

survivorship, rehabilitation, and end of life

issues. This balance must include attention

to the spectrum of distinct diseases we collectively refer to as cancer and the various

populations that experience these diseases

differently. We must not only balance

these pieces of the cancer research enterprise but link them through translational research.

In addition, we must rely on our diverse constituencies to help us identify new opportunities, gaps, and

barriers to progress, and to help us create new programs and improve existing ones.

Program Reviews

NCI supports research through a variety of 

mechanisms, many of which provide funds tailored

to specific research processes. As part of an ongoing process of review and revitalization, NCI has

instituted a series of external reviews to guide us

NCI’s Role in Cancer Research 19

NCI’s Role

Program Review

reports can be

found at 

http://deainfo.

nci.nih.gov/

advisory/

boards.htm
in strengthening our major research support programs. In the past few years, we have completed

in-depth reviews of several programs: Cancer

Centers, Cancer Control, Clinical Trials, Cancer

Prevention, and the Developmental Therapeutics

Program. 

Progress Reviews

One way NCI seeks the advice of experts is

through Progress Review Groups (PRGs) composed of prominent members of the scientific,

medical, and advocacy communities who

know the state of the science intimately

and can provide a thoughtful, considered

assessment of our portfolio and recommend activities that will speed our

progress. The overall goal of the PRGs is

to provide recommendations for a national cancer research agenda. PRGs meet

regularly over a period of months to

review an NCI-prepared analysis of the

Institute’s current research program,

review recommendations from the

research and advocacy communities,

define and prioritize unaddressed scientific opportunities that should be pursued,

and to develop a plan of action for the 

research area.

In the past year, PRGs in Breast and Prostate

Cancer completed their assessments of our

research programs and we have begun

considering and implementing their recommendations. A PRG in Colorectal

Cancer is planned for 1999. 

Implementing Recommendations

Program reviews, progress reviews, and

other assessment and advisory activities

conducted at NCI generate not only

insights, but also recommendations concerning how best to organize a program or

pursue a field of research. Implementing

these recommendations is key to successful planning, as planning alone does not

bring about change. To implement changes, we

have formed groups of outside scientists and NCI

staff that grapple with the redesign of programs

and development of new initiatives that are recommended by the Program Review Groups,

Progress Review Groups, and extraordinary opportunity Working Groups. Ongoing Implementation

Groups include those focused on Clinical Trials,

Prevention, Surveillance, Diagnostics, Tobacco

Research, and Early Detection.

SEEKING ADVICE

To ensure the wise use of resources to meet the

goals of the National Cancer Program,

NCI actively seeks out expert advice from

a variety of advisory bodies both within

and outside the Institute. 

National Cancer Advisory Board 

NCI’s principal advisory body is the

Presidentially appointed National Cancer

Advisory Board (NCAB). The NCAB,

with a membership including scientific

experts and advocates, advises NCI’s

Director on issues related to the entire

National Cancer Program and provides 

a second level of review for grant 

applications referred to NCI.

Board of Scientific Counselors 

The Board of Scientific Counselors (BSC) advises

the Institute leadership on the progress and future

direction of NCI’s Intramural Research

Program. These scientific experts from outside NCI, along with consumer advocacy

community representatives evaluate the

performance and productivity of NCI staff

scientists through periodic site visits to

intramural laboratories, and evaluate and

advise on the course of each Division’s 

programs.

Board of Scientific Advisors 

With the BSC, the Board of Scientific

Advisors (BSA) represents the scientific

community’s voice in the science NCI

conducts and supports. The BSA, composed of distinguished scientists from outside NCI and representatives from the consumer advocacy community, advises the NCI leadership on the progress and

20 The Nation’s Investment in Cancer Research

The Breast

Cancer Progress

Review report

can be found at:

http://wwwosp.

nci.nih.gov/

planning/prg/

bprgtableof

contents.htm

The Prostate

Cancer Progress

Review report

can be 

found at:

http://wwwosp.

nci.nih.gov/

planning/prg/

toc.htm
future direction of the Institute’s Extramural

Research Program. The BSA evaluates Instituteawarded grants, cooperative agreements, and contracts, and reviews ideas for new research solicitations to ensure that the concepts are meritorious

and consistent with the Institute’s goals.

NCI Executive Committee 

The NCI Executive Committee, which includes

NCI Division directors and other key advisors to

the Director, meets regularly to make major policy

and operating decisions for the Institute.

Director’s Consumer Liaison Group

Established in 1997, this first all-consumer 

advocate advisory committee at NCI consists 

of 15 consumer advocates who represent the

diverse face of consumer advocacy across the 

U.S. Its purposes are to:

■ Serve as a primary forum for discussing issues

and concerns and exchanging viewpoints

important to the broad development of 

NCI program and research priorities.

■ Help develop and establish processes, 

mechanisms, and criteria for identifying 

appropriate consumer advocates to serve 

on NCI program and policy committees.

■ Establish and maintain strong collaborations

between NCI and the advocacy community.

Community Input

Input from the community is very important to

NCI. So that we can better understand the needs

of cancer patients, those at risk for cancer, and

interested parties in the lay community, NCI

established the Office of Liaison Activities

(OLA). As NCI’s public liaison office, OLA fosters and enhances communication with this community and addresses the concerns of Congress

and the community about how NCI sets research

priorities. OLA maintains ongoing communications and information exchange between the

national cancer advocacy organizations and NCI,

encourages input and feedback from these organizations, and cooperates and collaborates with

these groups in areas of mutual interest. The

Office supports the Division of Extramural

Activities in expanding representation of consumer advocates on NCI peer review panels and

coordinates and supports the Director’s Consumer

Liaison Group. OLA also builds relationships with

professional societies and other Federal agencies,

and provides input and perspective to NCI on

complex issues relevant to cancer patients and 

the public.

The Consumer Advocate’s Role at NCI

Our work aims to support people with cancer, their families, their friends, and those at risk for developing the disease. We recognize this diverse community of people

affected by cancer as key stakeholders in our quest to conquer the disease, and we are including those who represent the voices of this community – consumer advocates –

in virtually all levels of NCI’s decision making processes.

Consumer advocates as members of NCI advisory committees and planning/oversight groups, play a vital role in

program planning and implementation and help to set priorities and research agendas. 

These advocates, often cancer survivors, provide the

patient’s view on a wide range of issues including those of

special concern to minority and medically underserved

populations. In addition, they often are advocate leaders

who have a broad view of the cancer problem and are

versed in the science. In 1999, NCI consumer advocates

participated in the review of grant and contract applications and in site visits and review committees. They also

provided ideas and recommendations for developing and

disseminating templates for new, easier to understand

informed consent documents. 

NCI’s Director’s Consumer Liaison Group and our other

consumer participation efforts, both coordinated through

our Office of Liaison Activities, have served as models for

the National Institutes of Health (NIH) community. 

NCI’s Role in Cancer Research 21

NCI’s Role
22 The Nation’s Investment in Cancer Research

I turned 50 this year. There’s no 

history of colorectal cancer in my

family, but my doctor said it’s time

to begin screening for the disease.

Frankly, I found the idea of it

embarrassing and, well...disgusting. 

Almost 130,000 people will be diagnosed with cancer of the colon or

rectum this year, and some 56,000

will lose their lives to these cancers.

Ninety percent of cases occur in

people older than age 50, but colorectal cancer can occur at any age.

Women and men are affected equally. Though mortality rates have been

declining slowly over the past 20

years, colorectal cancer is the second leading cause of cancer death in

America. Up to 90 percent of colorectal cancer deaths could be

avoided, but sadly, people avoid the

available screening tests. Screening

detects early cancers and the intestinal growths called polyps that can

become cancerous. When detected at

an early stage, colorectal cancer is

highly curable.

My friends who’d been screened 

had war stories to tell, but I decided

this was too important to put off. 

So I did it – I went for my colon

cancer screening. 

Colonoscopy is the standard for

screening. However, advances in

imaging may soon make colonoscopy

for initial screening unnecessary.

“Virtual” colonoscopy combines

imaging and computer technologies

to produce a three-dimensional

image of the entire colon. At this

point in its development, virtual

colonoscopy is

still not accurate enough for

use in routine

screening, but 

it is hoped that

continued

advances in the

required scanning and computer technologies will soon

make this 

possible.

Knowing that

many people

hesitate to

undergo screening, research is

underway to

find quicker, 

non-invasive ways of detecting colorectal cancer at its earliest stages.

For example, researchers are developing stool sampling methods able

to detect genetic changes that signal the presence of cancer. The p53

tumor suppressor gene and K-ras

cancer gene are known to be altered

in many colorectal cancers and can

be detected in stool. Other genes

have been discovered that identify

people with an hereditary or other

high risk of colon cancer; these

individuals need especially close

monitoring for early signs of cancer.

My doctor also explained the risk

factors for colorectal cancer and

what a person can do to reduce 

the risk of getting it. 

Risk factors for colorectal cancer

include a strong family history of

colorectal cancer or polyps (in a

first-degree relative – that is, parent

or sibling – younger than age 60 or

in two first-degree relatives of any

age); a personal history of colorectal

cancer, polyps, or chronic inflammatory bowel disease; or a family with

an hereditary colorectal cancer syndrome (e.g., familial adenomatous

polyposis, hereditary non-polyposis

colorectal cancer). If a person has

any of these known risk factors for

colorectal cancer, screening should

be considered earlier than age 50.

Genetic tests are available to identify family members with an inherited

predisposition to the disease. Since

nine out of ten cases of colorectal

cancers occur in those older than

50, aging also is considered a risk

factor for the disease. Smoking and 

People’s Story

Colorectal Cancer
NCI’s Role in Cancer Research 23

NCI’s Role

frequent consumption of alcohol and

red meat are associated with a higher colorectal cancer risk. 

Eating a diet high in fruits and vegetables and regular moderate exercise may reduce risk. Aspirin use and

hormone replacement therapy for

women after menopause each may

reduce colorectal cancer risk. Though

it is too soon to recommend that

people take supplements to prevent

colorectal cancer, limited research

suggests possible risk-reducing benefits of folic acid, vitamin E, selenium, and calcium supplements, as

well as a diet containing low-fat

dairy products. No one should begin

taking aspirin or supplements to prevent colorectal cancer without consulting a doctor first. 

There are certain symptoms that may

mean colorectal cancer. 

Symptoms, especially in people over

age 40, include a change in bowel

habits (constipation, diarrhea, black

or pencil-thin stools) that lasts more

than a few days; a feeling that you

need to have a bowel movement that

doesn’t go away after you do; rectal

bleeding or blood in stool; cramping

or gnawing stomach pain; decreased

appetite; weakness and fatigue; and

jaundice (yellowing of the skin or

white part of the eye). Symptoms

don’t mean you have cancer, but seeing a doctor is the only way to be

sure. Since a person also can have

no symptoms but still have colorectal cancer, the importance of regular

screening cannot be overstressed. 

I understand that colorectal cancer

treatments are improving, but I’m

going to keep up the screening and

do everything else I can to prevent it.

For people who do get colorectal

cancer, treatment and related care

that enhances quality of life are

improving. Thanks to surgical

advances, fewer patients now 

need permanent colostomies (a 

bag outside the body to hold waste 

after colorectal cancer surgery).

Chemotherapy for colorectal cancer

has improved; new agents and new

drug combinations are now available.

For patients whose cancer has spread,

chemotherapy can be given directly

into the artery that feeds the liver –

this may stop further spread of the

disease in the liver and increase survival for some patients. Other exciting treatments now in early clinical

trials include gene therapies designed

to deliver normal p53 genes into colorectal tumors and halt their growth,

and several approaches to boosting

the patient’s immune system to better fight colorectal cancer.

This vignette is a composite of 

experiences.

Colorectal Cancer Screening Tests

■ Fecal Occult Blood Test (FOBT) – The patient applies samples from three separate stools on consecutive days to a card. The card is sent to a laboratory to

check for any traces of blood. Many colorectal cancers cause minor bleeding

that would otherwise go unnoticed. Annual or biennial FOBT screening has

been proven to decrease the risk of dying from colorectal cancer.

■ Flexible Sigmoidoscopy – A lighted scope is inserted as far as the lower third

of the colon to check for growths, cancer, and inflammation. Performed in a

doctor’s office, the test takes about 10 minutes following bowel cleansing.

While it is 90 percent accurate, it does not examine the entire colon.

■ Colonoscopy – A lighted scope is used to visually examine the entire colon.

Usually performed on a hospital outpatient basis, colonoscopy takes about 

20 minutes after bowel cleansing. Any polyps found can be removed during

the test. This test is highly accurate.

■ Double Contrast Barium Enema – An x-ray of the colon is taken following

administration of a enema containing barium sulfate and expansion of the

colon with air; these two measures enhance the quality of the x-ray image.

■ Digital Rectal Examination – A doctor manually checks the lower part of the

rectum. This test is used to detect rectal and anal cancer.

To raise awareness that screening saves lives, NCI, the Centers for Disease

Prevention and Control, and the Health Care Financing Administration have

launched a public education campaign called Screen for Life. 
24 The Nation’s Investment in Cancer Research

T

he national cancer research program represents our Nation’s commitment to progress

against cancer through science. Science cannot thrive – indeed, it cannot even take place –

without the resources that support an enterprise 

of discovery. The engine that drives progress is 

the creativity, commitment, and hard work of

researchers and clinicians whose discoveries and

ideas are tested to find ways to understand, prevent, detect, diagnose, and treat cancer and to

care for the people who have cancer, have survived it, or are at risk.

SUPPORTING OUR RESEARCH

In support of the community of cancer researchers,

NCI has built an infrastructure, or framework, of

support mechanisms, organizations, and networks

that link scientists, facilities, and information. It is

this infrastructure that NCI’s budget supports.

Extramural Research

NCI’s Extramural Research Program serves as our

link to the greater scientific community and

includes the Divisions of Cancer Biology, Cancer

Treatment and Diagnosis, Cancer Prevention, and

Cancer Control and Population Sciences. An

essential component of the Extramural Research

Program is NCI program staff. Their scientific

expertise in cancer-related fields and national

focus in a given research area enables them to

work effectively with NCI-funded scientists in

academia and industry to facilitate research

progress. They synthesize the state of the science

in important areas, identify priorities for new

research directions, foster collaborations among

scientists, keep abreast of the research program

through active communication with investigators,

organize scientific meetings to promote the interchange of information among investigators, and

secure supplemental funds as deemed meritorious.

Program staff are a resource for researchers, educating them on NCI policies and procedures,

advising scientists new to the NCI system on the

preparation of research grant applications, and

reviewing and identifying gaps in our research

portfolio that may lead to new areas of research

emphasis. Finally, program staff monitor the

progress of extramural grants through contact with

individual investigators and annual research

progress reports. Results of these NCI-funded projects are communicated to the scientific community and the public primarily through peer reviewed

scientific journals, but also through major scientific meetings, workshops, and symposia, and

through our other cancer communication outlets,

How We Work

How We Spend Our Budget

■ About 73% of our budget supports basic and clinical

studies conducted by researchers and clinicians across

the Nation through our Extramural Research Program.

■ We spend about 16% of our budget on our Intramural

Research Program, in which NCI’s own scientists 

conduct cancer-related research.

■ About 4% of our budget is devoted to training, 

education, and career development of researchers 

and clinicians at every stage of their careers.

■ We use about 3% of our budget to communicate 

the latest information about cancer risk, detection,

prevention, treatment, rehabilitation, and control 

to people with cancer, health professionals, and 

the general public.

■ About 4% of our budget supports the administration

and management of the Institute. 
such as the Cancer Information Service, the

Physician Data Query database, our press office,

and our Web site.

Research Project Grants 

The main pool of funds expended by NCI

for awards to extramural scientists is known

as the Research Project Grant (RPG) pool.

These funds foster the creativity of talented

scientists by providing them with the freedom to pursue the best ideas that will yield

progress against cancer. 

NCI funds two main types of research

project grants: Single Research Project

Grants, awarded to institutions on behalf

of individual principal investigators, and

Program Project Grants, funded to foster

collaborations among groups of scientists

involved in related research projects. In

FY 2000, NCI anticipates expending more than

$1.4 billion in support of over 4,300 separate

research grants. More than 1,150 of these awards

will be new or competing renewal projects. The

single investigator grant payline rose from the

15th percentile in FY 1995 to the 24th percentile

in FY 1999. These grant awards and the

dedicated researchers behind them constitute the largest single categorical investment of resources that NCI, through the

extramural research community, makes

annually to combat cancer. Collectively,

the Single Research Project and Program

Project Grants span the full range of

basic, clinical, population-based, and

translational studies of cancer etiology,

biology, prevention, detection, diagnosis,

treatment, control, and survivorship. The

advances that come from these investments, such as the discovery and development of paclitaxel (Taxol®) and tamoxifen (Nolvadex®), and advances in the

understanding of basic bone marrow transplant

biology and clinical application, represent the

future of cancer research and cancer care.

Other Grant Mechanisms 

NCI also has special mechanisms for exceptionally

high-risk, innovative, exploratory, and developmental research activities, to allow investigators to

embark on projects of unusual scientific potential,

and to support research and development ideas

that are likely to result in the development of a

commercial product or service.

Support for Extramural Clinical Research 

Clinical research is one of the cornerstones of the

National Cancer Program. Every new treatment

we use today, every preventive measure that is

widely recommended, and every innovative detection strategy was, at one time, tested in cancer

How We Work

How We Work 25

A complete 

listing and

description of

NCI’s grant

mechanisms can

be found at

http://deainfo.

nci.nih.gov/

flash/awards.

htm

Research Project Grants (RPGs)

(dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

Ongoing $983,129 $1,056,342 $1,166,993

New 377,516 353,517 366,244

Subtotal 1,360,645 1,409,859 1,533,237

Small Business 57,808 60,978 63,173

Innovation 

Research

TOTAL $1,418,453 $1,470,837 $1,596,410
patients or in people at risk for the disease. These

heroes of the fight against cancer have allowed us

to amass the body of information we are building

upon every day. Even though trials often test the

latest therapies, there is no guarantee of success –

a person may be randomly assigned to a control

group to receive standard therapy, or may participate in a Phase I or II trial which may be too early

in the drug’s development to know if it is effective. Nonetheless, trials provide patients and other

participants access to cutting-edge interventions

and provide researchers with information that ultimately will enable us to prevent and effectively

treat all cancers.

A strong clinical research infrastructure, including a comprehensive program of clinical trials in

treatment, early detection, and prevention, is a

vital component of NCI’s research program. NCI’s

Cancer Centers, Cooperative Groups, and

Community Clinical Oncology Program are where

findings from the laboratory are translated into

new treatments, diagnostic tools, and preventive

interventions, and where these measures are first

tested for safety and effectiveness. These programs

are fundamentally interrelated: every Cancer

Center is a participant in at least one Cooperative

Group, and Cooperative Groups serve as research

bases for participants in the Community Clinical

Oncology Program. Hundreds of clinical trials are

supported through these and other research mechanisms, such as Single Research Project Grants,

Program Project Grants, cooperative agreements,

and contracts. 

NCI’s programs in clinical research have

enjoyed many notable successes over the years.

NCI has been responsible for the early development and/or testing of many important treatments, including paclitaxel (Taxol®) for breast

and ovarian cancer, interferon alpha-2b for malignant melanoma, and Herceptin® for breast cancer. Studies to test the effectiveness of certain

drugs to prevent first occurrences of cancer

include the ongoing Prostate Cancer Prevention

Trial. The Breast Cancer Prevention Trial demonstrated a 49 percent reduction in breast cancer

incidence during the treatment period among

high-risk participants who took the drug tamoxifen (Nolvadex®). Based on the results from that

trial, the Food and Drug Administration has

approved the use of tamoxifen to reduce the

chance that women at high risk of breast cancer

will develop the disease.

Through our clinical research programs, we also

have identified successful interventions for symptom management and continuing care of cancer

patients, including treatment for mouth sores and

hot flashes, both common side effects of

chemotherapy. And based on the results of laboratory research, we now are exploring interventions

for individuals whose genetic profile places them

at increased risk of cancer.

However, our ability to conduct clinical trials is

in danger of being compromised by changes in the

health care system. In the past, institutions have

used surplus revenues from patient care services to

supplement government research support. The

growth of managed care has all but eliminated

those discretionary funds. As a result, institutions

can no longer sponsor research activities requiring

capital expenditures and cannot support essential

training for young investigators. These changes

pose a very real danger for the continuation of

cancer research and our continued progress against

cancer.

In response to the changing health care system,

we are developing ways to improve access to and

participation in clinical trials. To ensure that

physicians have the time to conduct clinical trials,

26 The Nation’s Investment in Cancer Research

Clinical Trials Infrastructure

(dollars in thousands)

1999 2000 2001 

Operating President’s Core

Budget Budget Budget

TREATMENT:

Clinical $126,205 $125,460 $129,977

Cooperative 

Research

Community 6,565 6,007 6,009

Clinical Oncology

Program

Subtotal 132,770 131,467 135,985

Treatment

PREVENTION:

Community 45,596 48,305 50,258

Clinical Oncology

Program

TOTAL $178,366 $179,772 $186,244
How We Work 27

How We Work

What are Clinical Trials?

Clinical trials are research studies conducted to answer

specific scientific questions about new ways to prevent, diagnose, detect, and treat cancer. Most clinical trials are designed to test new cancer treatments; concurrent

or separate studies also may look at the psychological

impact of cancer or ways to improve a patient’s quality of

life. In addition, the number of clinical trials to test drugs

for cancer prevention has been increasing, because of success with large precedent-setting prevention trials, such as

the Breast Cancer Prevention Trial.

Before a clinical trial of a promising new treatment or

preventive agent can be launched, the agent must undergo

rigorous laboratory testing to prove that it may be beneficial to patients and will be safe to use during testing. 

If the agent is promising and is safe for use, then

researchers design a trial in an effort to answer a specific

scientific question about the agent’s use or efficacy. The

researchers then establish strict entry criteria to help

identify patients who are best suited for the trial. Only

then can the researchers recruit volunteers to participate.

Trials generally are conducted in three phases: 

■ Phase I — These are small trials designed to tell

researchers how best to administer the new intervention and, in studies of new agents, the optimal dose of

the drug to give with the least possible side effects.

■ Phase II — Involving a small number of people,

these studies determine if the treatment, delivered at

the optimum dose, destroys or prevents cancer and

against what types of cancer it works best.

■ Phase III — Once a new therapy has been proven to

have an anti-cancer effect and be safe, it then moves

to a Phase III trial to compare its efficacy with that of

a standard therapy. Phase III trials often are large, and

may include hundreds or thousands of people from

across the country.

As each phase of testing is completed, the data collected are analyzed and the results published. Based on

this analysis, the researchers determine whether the agent

is showing enough of a benefit to continue testing. Once

a therapy has successfully completed these three phases of

testing, a New Drug Application is submitted to the U.S.

Food and Drug Administration. The testing and approval

process can take many years; however, the approval

process can sometimes be accelerated, particularly if the

agent is beneficial for patients with a form of cancer that

has few treatment or prevention options. Occasionally,

additional trials (called Phase IV trials) are conducted

after the approval of the drug to provide longer-term 

safety data or to collect new types of information, such as

quality of life assessments.

Ensuring Diversity in Clinical Trials

Participation 

E nsuring participation in clinical research, particularly

among women and members of special population

groups, is a high priority for the Institute; several programs help us ensure that all populations are well represented. The Minority-Based Community Clinical Oncology

Program, begun in 1990, has been successful in accruing

minority cancer patients to trials and provides for studies

in minority populations that may lead to better understandings about the dynamics of patient accrual. In addition, two new grant programs are supporting research on

ways to draw more women and minority participants into

prevention and screening studies. The Institute also has

funded a number of conferences aimed at sharing current

information and strategies to maintain and enhance its

good record of minority accrual to clinical trials. 

As a result of our efforts, analysis of accrual patterns

in Cooperative Group cancer treatment trials has shown

that women and ethnic/racial minorities are proportionally

represented in NCI cancer treatment trials. Nearly 20 percent of the more than 20,000 patients entering treatment

clinical trials every year are members of an ethnic/racial

minority group. 

Understanding Clinical Trials
28 The Nation’s Investment in Cancer Research

we have developed a Midcareer Investigator

Award in Patient-Oriented Research that offers

subsidies to clinicians, allowing them protected

time to devote to vital patient-oriented research.

Further, through agreements with private insurers

and other government agencies, we are working to

assure insurance coverage for individuals participating in trials. We have two government interagency agreements, one with the Department of

Defense (DoD) that provides coverage for DoD

health plan beneficiaries to participate in NCIsponsored cancer treatment trials, and a

second with the Veteran’s Administration

that covers the full range of NCI-sponsored clinical trials. This year, we signed a

new agreement with the DoD, marking

the first time a health plan has agreed to

provide coverage for participation in cancer prevention trials. Based on these initial successes, several organizations have

enacted agreements at the local, state,

and national levels to provide greater

access and coverage for clinical trials. For

example, in 1999 the United Health Care

Corporation began piloting a program

providing coverage of the patient care

costs associated with cancer treatment trials conducted by the NCI-supported

Coalition of Cooperative Groups. Several

states also have enacted legislation

designed to provide greater access and coverage for

clinical trials. In addition, NCI is working with

patient advocates, local communities, and nonprofit organizations to increase awareness of and

education about clinical trials. Together with

other clinical trials efforts, we hope these initiatives will serve as national models and provide

access for more individuals interested in participating in clinical trials.

Cooperative Group Clinical 

Trials Program

The sheer number of different types of cancer and

their biological complexity make the process of

efficiently identifying and evaluating new treatments or other anti-cancer strategies extremely

challenging. To test potential treatment advances

in patients more rapidly, NCI maintains the

Cooperative Group program, a national network

of 12 consortia (Cooperative Groups) that seek to

define the key unanswered questions in cancer and

then conduct clinical trials to answer them. Each

year, 1,700 institutions throughout the United

States and Canada, and approximately 8,000

investigators in these institutions participate in

these trials. This kind of cooperation makes it possible to centralize administration and data collection for trials taking place at a large number of

sites around the world. The Cooperative Groups

differ in structure and research organization, but

they share the common purpose of developing and conducting large-scale trials in

multi-institutional settings. 

Cooperative Groups frequently work

together when the cancer in question is so

rare that one group working alone would

be unable to accrue enough patients to

conduct a meaningful study. For example,

six Cooperative Groups worked together

on the landmark study establishing that

all-trans retinoic acid (ATRA) significantly improves disease-free survival time for

patients with acute promyelocytic

leukemia. Cooperative Groups collaborate

regularly on clinical trials for solid tumors

in children, breast cancer, colorectal 

cancer, lung cancer, prostate cancer, and

cancers of the head and neck. 

Approximately 20,000 patients participate in Cooperative Group clinical trials each year,

principally in large Phase III trials that help establish the state of the art for cancer therapy. Many

new anti-cancer drugs are tested in patients for the

first time under NCI Investigational New Drug

(IND) sponsorships through the Cooperative

Group program. Nearly 200 investigational agents

or treatment strategies, ranging from new

chemotherapy drugs and cancer vaccines to agents

that prevent tumor blood vessel development, are

currently being studied under NCI INDs. 

An agreement between the U.S. Office for

Protection from Research Risks and the European

Organization for Research and Treatment of

Cancer (EORTC) promises to improve the ability

of NCI’s Cooperative Groups to collaborate with 

the EORTC and other international cancer

research groups. 

To learn more

about the

Cooperative

Group program,

visit the

Cooperative

Group Web 

site at

http://ctep.

info.nih.gov/

CoopGroup/

Coop_Group_

Prog.html
How We Work 29

How We Work

Community Clinical Oncology

Program (CCOP)

The Community Clinical Oncology

Program is a network of 49 central offices

in 31 states that provides the infrastructure to link more than 2,500 community

cancer specialists and primary care physicians with clinical Cooperative Groups

and Cancer Centers. In addition, CCOPs

support scientific development and the

implementation of ongoing cancer treatment, prevention, and control clinical trials among community Cooperative Group

members and Cancer Centers. 

This network enables individuals to

participate in state-of-the-art clinical

research trials at over 340 community

hospitals without the burden of traveling

to a distant site. Each year, the Program

enrolls more than 5,000 patients in cancer

treatment clinical trials and an additional

3,500 patients in cancer prevention and control

clinical trials. An additional seven Minority-based

CCOPs increase the participation of

minority individuals in clinical trials

research. Each year, over 700 patients

enter clinical trials through these specialized CCOPs. Located in six states and

Puerto Rico, these programs bring an

additional 33 hospitals and 250 physicians

into the clinical trials network. By

increasing the number of patients and

physicians who participate in clinical trials, the program helps transfer the latest

research findings to the community.

Cancer Centers 

Fifty-nine research-oriented institutions throughout the Nation have been designated NCI-supported Cancer Centers in recognition of their scientific excellence. The Centers are key partners in

NCI’s efforts to speed the process of discovery and

bring the benefits of cancer research directly to

the public. Located throughout the country, each

Cancer Center is a hub of cutting-edge research,

high quality cancer care, and outreach and education for both health care professionals and the

general public. 

When an institution meets the rigorous competitive standards to become an NCI Cancer

Center, it is awarded a Cancer Center

Support Grant. These funds enable the

institution to coordinate multidisciplinary

approaches to research questions, to gain

access to the most advanced research

technologies, and to take rapid advantage

of new research opportunities. Support for

the Cancer Centers helps ensure a close

association between state-of-the-art

research and state-of-the-art care activities within the institution. Moreover, it

allows each Center to develop key collaborations with industrial, community, and

state health organizations, and to link the

research capabilities and expertise of scientists within the institution to problems

of cancer incidence and mortality in their

communities and regions. 

Three types of centers exist: Cancer

Centers have specific research foci, such

as epidemiologic or basic research;

Clinical Cancer Centers integrate basic science

with clinical science; and Comprehensive Cancer

Centers demonstrate both significant scientific strength in basic, clinical, and

population studies and strong interdisciplinary collaboration. Comprehensive

Cancer Centers also must have in place

effective cancer information, education,

and outreach activities for the regions and

communities they serve. 

Traditionally, Cancer Centers have had

broad scientific bases, and most have been

developed within a single institution.

Changes in the program, however, are

Cancer Centers (dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

Basic $13,504 $18,765 $19,441

Clinical/ 134,738 137,014 141,947

Comprehensive

Subtotal 148,242 155,779 161,387

Core Grants

Planning 1,131 787 815

SPOREs (P50) 48,117 40,889 42,361

TOTAL $197,490 $197,455 $204,563

More information

on the

Community

Clinical Oncology

Program is 

available at

http://dcp.nci.

nih.gov/corb/

CCOP.html 

The Minoritybased CCOP Web

site is located at

http://dcp.nci.

nih.gov/corb/

MBCCOP.html

The Cancer

Centers program

Web site is

located at

http://www.nci.

nih.gov/

cancercenters/
enabling the planning of new consortia of institutions, often linking free-standing clinical and academic centers with community hospitals to form

networks with tremendous research strength and

the ability to deliver quality care in a managed

care environment. In addition, more focused scientific concepts are being developed for Cancer

Centers. For example, some Centers are focusing

on population sciences and others are concentrating on translational research opportunities within

a specific scientific discipline, such as immunology. Overall, such changes in the Cancer Centers

program promise to increase the scientific versatility, translational research capabilities, and geographic distribution of NCI-supported Cancer

Centers.

Intramural Research 

The NCI Intramural Research Program (IRP),

consisting of more than 400 principal investigators

in the Divisions of Basic Sciences, Cancer

Epidemiology and Genetics, and Clinical

Sciences, is dedicated to the comprehensive

understanding of cancer and to finding cures for

these diseases. Organized to complement ongoing

research in universities and in industry, the IRP

has been involved in pivotal discoveries in cancer

research: the first successful treatments for childhood leukemias; establishing the principles for

curative chemotherapy for lymphomas; developing

effective therapies for HIV; defining the foundations for tumor vaccines; identifying the genetic

causes for familial cancers; and uncovering environmental causes of cancer. 

The IRP’s epidemiology research program is a

national program of population-based studies to

identify environmental and genetic determinants of

30 The Nation’s Investment in Cancer Research

Intramural Research 

(dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

Basic $173,218 $172,602 $179,506

Clinical 117,039 116,623 121,288

Epidemiology 48,987 48,823 51,156

& Genetics

NIH Central 149,640 149,097 154,681

Services

TOTAL $488,884 $487,144 $506,630

SPOTLIGHT ON RESEARCH

NCI’s Intramural Program

NCI’s Intramural Research Program (IRP) is a critical part of the effort to understand and find cures

for the many types of cancer. New programs include:

Our recently established Advanced Technology Center

(ATC), home to the Cancer Genome Anatomy Project

(CGAP), two high throughput genotyping and sequencing centers, and a microarray facility, that uses new

technologies to address biological, clinical, and genetic

questions pertinent to human cancers. The ATC, which

focuses on clinical and molecular medicine, houses

investigators from NCI and from the National Human

Genome Research Institute, whose research centers on

human cancer genetics, molecular epidemiology, and

cell biology. Through the efforts of CGAP and array projects, ATC has become a premier facility for the development of tools for molecular expression profiling studies.

NCI is initiating a joint effort with the National Institute

of Neurological Disorders and Stroke to develop a NeuroOncology Branch at the NIH Clinical Center. Researchers

will study both adult and childhood brain tumors from a

translational perspective, applying advances in the

understanding of the basic biology of central nervous

system malignancies to novel, targeted treatments.

In support of NCI’s long tradition of using mice as 

models for human cancers, a new Mouse Genomics

Program will bring together scientists with varied but

related expertise in the field to create an environment

for rapid progress in this area. The program will develop

new disease models based on advances in the development of high-resolution genetic and physical linkage

maps of the mouse genome, transgenic technology, and

array technologies. These models will offer a potentially

important resource for preclinical testing of different

treatment strategies.
cancer. This IRP component supports epidemiologic and interdisciplinary research to ensure that the

momentum of recent and ongoing discoveries in

molecular genetics and cancer biology is accelerated

and broadened through population-based studies

into the etiology of cancer and its prevention.

The intramural clinical research program is

conducted principally in NIH’s Warren G.

Magnuson Clinical Center. It provides the opportunity for patients from across the country to be

treated through ground-breaking research protocols. The Clinical Center is a unique environment

in which investigators throughout the NIH community develop and test novel therapies derived

from our growing body of knowledge; in this environment new information can be transferred

quickly from the laboratory to the patient and

back to the laboratory for additional

analysis. 

The Intramural Research Program is

uniquely structured to address cancer

research problems whose resolution

requires long-term commitments and that

may be considered unsuitable for many

extramural funding mechanisms. Another

unique aspect of the Intramural Program

is its framework for cooperation between

basic researchers and investigators performing clinical trials. These interactions, fostered

by common research interests, topic-specific focus

groups and retreats, and close physical proximity

of basic and clinical research efforts, result in rapid

translation of new basic research discoveries into

early clinical trials. 

Because of its national stature and unique structure, NCI’s IRP also is a center for basic, clinical,

and population-based oncology training for

researchers, clinicians, research fellows, and visiting scholars from around the world. NCI plays a

major role in fostering the education and careers

of a growing number of nurses, doctors, and physician assistants, as evidenced by the approximately

500 participants each year in the summer intramural research training program. Many of the current

leaders in cancer research received some of their

training at NCI, and we anticipate that the IRP

will continue to be an important resource for

training the next generation of investigators.

Cancer Control 

Cancer control research encompasses basic and

applied research in the behavioral, social, and

population sciences aimed at creating or enhancing interventions that, by themselves or in combination with biomedical approaches, reduce cancer

risk, incidence, morbidity, and mortality, and

improve quality of life. For example, a cancer control study might investigate the use of a medical

intervention, such as a nicotine patch, in combination with a behavioral intervention, such as a

counseling program to help smokers overcome

their barriers to quitting. Interventions may be

directed at patients, physicians, and/or other

health care providers. Cancer control research

seeks to improve interventions across the human

lifespan and over the entire cancer continuum,

and to move research findings into clinical and public health practice. The foundation of cancer control research is epidemiology, and surveillance and outcomes

research are the fundamental mechanisms

for assessing progress.

NCI maintains a firm commitment to

cancer control research through the

Division of Cancer Control and

Population Sciences (DCCPS), the focus

for NCI-sponsored research programs

aimed at studies in populations, behavior, surveillance, special populations, outcomes, and other

aspects of cancer control. Our wide-ranging cancer

control research efforts include research in epidemiology and genetics, tobacco research, tailored

communications, and theoretical models for studies of human behavior and behavior change.

How We Work

How We Work 31

For more 

information on

the NIH Clinical

Center visit

http://www.cc.

nih.gov

Cancer Control 

(dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

Grants $107,549 $113,671 $127,734

Contracts 103,828 116,408 120,599

Cancer Control 89,882 82,640 85,946

Management & 

Support

TOTAL $301,259 $312,719 $334,278
Cancer surveillance – tracking and analyzing

trends in cancer incidence, mortality, and survival

rates – is a critical component of cancer control.

The keystone of NCI’s surveillance efforts is the

Surveillance, Epidemiology, and End Results

(SEER) program, which monitors the Nation’s

cancer burden and provides the basis for assessing

individual, organizational, and societal factors that

can reduce cancer rates. (See page 92 for further

information on cancer trends.) 

AIDS Research

Malignancies occur in more than 30 percent of

AIDS cases and contribute greatly to AIDS morbidity and mortality. Many areas of fundamental

biology developed in NCI programs, including

virology, immunology, and cellular and molecular

biology, are directly applicable to understanding

HIV and AIDS. Research efforts in AIDS malignancies begins with basic science that provides

new insights in cancer biology that can lead to

hypotheses to test in epidemiologic studies, the

development of treatment targets, and new treatments to prevent and control AIDS malignancies.

But basic science, even with associated drug development programs, would not make progress without clinical programs in which to test potential

discoveries. Work in this area is necessarily collaborative and one of NCI’s major roles is to foster

these collaborations, create research groups, and

provide infrastructure, including clinical trials support, central specimen banking, international scientific meetings, and new investigator training. 

Today, research into the fundamental biology of

HIV and AIDS, AIDS treatment, and particularly

AIDS-related malignancies takes place throughout

all programmatic mechanisms of NCI. The

Intramural Research Program is an internationally

recognized center for research in HIV and AIDS,

housing the HIV Drug Resistance Program, the

HIV and Malignancies Branch, and the NIH

Vaccine Research Center, a joint project with the

National Institute of Allergy and Infectious

Diseases. The Extramural Research Program also

has been a vital and innovative force in this area

of research. Among its programs are the AIDS

Malignancy Consortium, the AIDS Malignancy

Bank, the AIDS Oncology Clinical Scientist

Training Program, and an annual international

forum on AIDS malignancies.

NCI, in coordination with other NIH Institutes

and the NIH Office of AIDS Research, continues

its commitment to meeting the challenge of AIDS

and is working to ensure that NCI-supported

AIDS and AIDS-related research is integrated

with national AIDS strategies.

Training and Education 

In the past decade, we have made stunning

advances in our understanding of cancer. Our ability to bring these new discoveries to the communities and clinics where they benefit cancer patients

and those at risk for developing cancer depends on

physicians and other scientists who are specially

trained in cancer research. While resources for

training are shrinking at many institutions, NCI is

committed to ensuring that a national cadre of

trained cancer researchers exists by continuing to

provide essential training to our Nation’s scientific

and medical workforce. 

To address this crucial requirement, NCI has

developed a strategic plan for extramural training,

education, and career development. This plan

focuses on attracting young scientists into cancer

research, on providing stability and protected

research time for researchers in disciplines critical

to translational research, on creating more opportunities for underserved ethnic and minority scientists, and on encouraging research program diversification. In pursuit of these objectives, NCI has

32 The Nation’s Investment in Cancer Research

Training and Education

(dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

National Research 57,135 58,026 60,115

Service Awards

Research Career 34,881 38,915 40,316

Program

Cancer Education 17,319 16,692 17,293

Program

Minority 2,788 3,623 4,373

Biomedical 

Research Support

TOTAL $112,123 $117,256 $122,097
implemented a number of new training and career

development programs in basic, clinical, population, and diversified sciences, as well as for underserved ethnic and minority groups who are underrepresented in the research workforce. These programs aid investigators in stabilizing and sustaining productive research careers, and offer opportunities for engaging in translational research (see

page 96 for more information on training).

NCI’s research divisions also are developing

training programs. For example, the Division of

Clinical Sciences’ Clinical Intramural Research

Award supports innovative and collaborative clinical research projects emphasizing novel approaches or promising new outcomes of current research;

the Division of Cancer Epidemiology and

Genetics’ Cancer Genetics and Epidemiology

Fellowship Program provides interdisciplinary

training in clinical, molecular, and quantitative

genetics, and genetic epidemiology; and the

Division of Cancer Prevention Fellowship provides training in cancer prevention and control for

individuals from many health science disciplines.

Other Research Support 

In addition to its many types of grants and awards,

NCI employs a variety of other research support

mechanisms. These mechanisms include: contracts

to provide support for research, information 

Informing Professionals 

and the Public — 

NCI’s Information Services

Every day, thousands of people – health professionals,

cancer patients and their families, and the general

public – benefit from NCI’s broad array of information

and public education services. Using basic printed 

materials, sophisticated Internet technology, and

everything in between, NCI provides millions of people

each year — often in Spanish as well as English —

with the complete, reliable information they need to

make decisions about cancer prevention, detection,

treatment, and follow-up care. NCI’s services include: 

■ The Cancer Information Service (CIS). This nationwide cancer information and education network,

available in all 50 states, Puerto Rico, and the U.S.

Virgin Islands, receives more than 2,000 calls each

day. By calling 1-800-4-CANCER (1-800-422-6237),

cancer patients, their families, people at risk for 

cancer, and health professionals can receive information confidentially on all aspects, including prevention, treatment and clinical trials. Callers with 

TTY equipment can dial 1-800-332-8615.

■ NCI’s Internet Services. Patients and health professionals with access to the Internet may search for

accurate, up-to-date information about cancer on:

NCI’s Web site (http://www.nci.nih.gov) or the

International Cancer Information Center’s CancerNetTM

Web site (http://cancernet.nci.nih.gov) and

cancerTrialsTM (http://cancertrials.nci.nih.gov).

■ Physician Data Query (PDQ®). The CancerNetTM

searchable PDQ® data base contains current information on cancer prevention, screening, treatment,

and supportive care, as well as descriptions of

active clinical trials and directories of physicians,

health professionals who provide cancer genetics

services, and organizations involved in cancer care.

■ CANCERLIT®. This bibliographic data base contains

more than 1.4 million records on cancer literature

from 1963 to the present. It can be searched from

the CancerNetTM Web site.

■ The PDQ/CANCERLIT® Service Center. Physicians

and other health professionals can make requests

for PDQ and CancerLit information through a tollfree telephone service (1-800-345-3300), e-mail

(cancermail@icicc.nci.nih.gov with the word

“help” in the body of the message, users receive a

contents list and ordering instructions by return

electronic mail.), or fax (301-402-5874).

■ Print Publications. NCI makes available nearly 

600 publications and audiovisual materials, many

published both in English and Spanish. They are

available from the toll-free number 1-800-4-CANCER

or from the NCI Web site. NCI is also working to

develop materials in several Asian languages. 

How We Work

How We Work 33

Other Research Support

(dollars in thousands)

1999 2000 2001

Operating President’s Core

Budget Budget Budget

Research $275,087 $298,569 $309,519

Support Contracts

Scientific 3,528 3,742 3,877

Evaluation Grants

Research 19,437 21,338 22,106

Resource Grants

Construction 3,000 3,000 5,000

Conference Grants 901 1,101 1,141

Research 108,965 110,065 114,468

Management 

& Support

TOTAL $410,918 $437,815 $456,111
34 The Nation’s Investment in Cancer Research

SPOTLIGHT ON RESEARCH

Addressing the Unequal Burden of Cancer —

Special Populations Research

Not all populations are affected equally by cancer.

Cancer statistics and numerous studies have shown

that some population groups develop cancer more often,

have poorer survival, and are more likely to die from

cancer than others. These “special” populations, which

are not mutually exclusive, include ethnic minorities,

geographically isolated and other medically underserved

populations, the elderly, women, people of diverse cultures and lifestyles, and people with lower income, education, and literacy levels. We know that major differences in cancer burden exist between these groups and

the general population. Moreover, disparities exist within and between special populations, who likewise are

affected more severely by many specific types of cancer.

Research also is demonstrating that differences in cancer morbidity and mortality previously attributed to race

are not due to supposed biological differences between

populations or between the tumors individuals develop.

Rather, these differences actually reflect the too-frequent biological and medical consequences of sociallydefined race – lower socioeconomic status and educational level, and less access to high quality cancer care.

For example, recent data from NCI’s Black-White Study

of Cancer Survival showed that compared with white

women, black women with breast cancer (as well as

poor and older women) were less likely to receive

appropriate treatment after diagnosis. They also are

more often diagnosed at a later stage of disease and are

less likely to have a regular source of health care.

Similar disparities in appropriate treatment have been

demonstrated between various population groups with

prostate, lung, colorectal, and cervical cancers. Analyses

of NCI clinical trials have shown however, that equal

treatment yields equal outcome, and that race is not a

factor when there is equal treatment.

NCI has long supported and is committed to a broad array

of research and related activities to pinpoint, understand,

and address cancer disparities. NCI plans and coordinates

these activities through organizational units dedicated to

special populations issues. The Office of Special

Populations Research was established in 1996 to advise

the Director of NCI and provide a focal point for leadership and coordination on minority and other special populations research. NCI’s Comprehensive Minority

Biomedical Branch creates and coordinates programs to

broaden participation in all aspects of cancer-related

research and training activities by minorities and other

special populations. The Applied Sociocultural Research

Branch (ASRB) promotes grant-supported cancer prevention and control research in populations that experience a

greater burden of cancer. The ASRB also offers training to

help potential applicants prepare scientifically competitive

research applications in cancer control science. Special

populations initiatives at NCI now are expanding even further to encompass a larger spectrum of special populations, and to create new opportunities to attract and train

cancer researchers and clinicians from special populations. 

For more than 20 years, NCI’s Surveillance, Epidemiology,

and End Results (SEER) cancer registry program has monitored the Nation’s cancer burden and been a world model

for tracking population trends in cancer incidence, survival, morbidity, and mortality. SEER data are used by

researchers to develop studies designed to explain cancer

trends and identify study populations, by health planners

and policy makers at all levels, by public health practitioners, and by the public. SEER now is being expanded to collect data on a wider range of population subgroups and on

socioeconomic and other factors that underlie cancer

trends. As many as four new state registries will be added

to SEER, and up to ten additional states will receive supdissemination, and management; conference

grants to fund meetings, conferences, and workshops; resource-related research projects to

improve the ability of resources to serve biomedical research; scientific evaluation awards to support the scientific review of grant and contract

proposals; and construction grants and contracts

to provide partial support for the modernization or

development of cancer research facilities throughout the Nation. 

NCI also sustains, guides, and monitors both

the extramural and intramural activities of the

Institute through its research management and

support activities. These activities include overall
How We Work 35

How We Work

plementary funding to upgrade their existing registries to

meet SEER standards. This expansion will be achieved in

partnership with the Centers for Disease Control and

Prevention, and will capture data on a broader spectrum 

of Native American and Hispanic population subgroups,

rural African Americans and whites, and others.

NCI recently launched the Special Populations Networks

for Cancer Awareness Research and Training, for which

$30 million has been earmarked over five years. Funding a

diverse group of research projects aimed at improving

cancer prevention and control in minority and underserved

communities, the Networks will build upon and expand

the scope of NCI’s three National Leadership Initiatives

that now are drawing to a close. The Leadership

Initiatives were instrumental in launching collaborative

efforts to raise cancer awareness, improve access to care,

and reduce the cancer burden in African American,

Hispanic, and Appalachian populations. Principal goals of

the new Networks will be to develop and maintain partnerships between scientific researchers and community

leaders in a broader range of minority and underserved

populations, develop and test community cancer awareness activities, support minority enrollment in clinical trials, and encourage minority scientists to participate in

research. Initial awards under the program will be made in

March 2000.

Also responding to the need to attract, develop, and support researchers and cancer care givers from minority and

underserved populations, NCI recently organized and

expanded special populations biomedical training opportunities under the Continuing Umbrella of Research

Experiences (CURE) initiative. CURE reaches minority

students as young as high school age, develops undergraduate, graduate, and postdoctoral scientists, and supports young minority investigators as they establish their

research careers. CURE also provides training support for

individuals with disabilities and for scientists re-entering

an active research career after taking time off for child

care or other family responsibilities. In addition, longterm partnerships between NCI Cancer Centers and

both minority and minority-serving institutions are

being established. The partnerships are expected to

enhance the cancer centers’ approaches to outreach and

education for underserved communities as well as the

institutions’ approaches to conducting cancer research and

training future cancer scientists.

In July 1999, NCI convened a meeting of key staff and

identified experts to discuss how best to describe underserved populations to aid NCI in planning, research, and

related activities to address cancer issues in these populations. In addition, NCI has appointed a Special

Populations Working Group to enhance its prioritysetting and information dissemination processes and

strengthen communication with the many groups, organizations, and institutions involved in special populations

issues. Its membership is drawn from a variety of medical

and non-medical disciplines, individuals knowledgeable

about the cancer experience, and diverse communities.

The Working Group is charged to raise and articulate special populations concerns and issues, make recommendations for addressing special populations issues at the NCI,

suggest NCI-community partnerships to reach common

goals, and provide an ongoing communication channel

with diverse minority and special populations communities. This important group met for the first time in May

1999 and will meet approximately three times per year.

scientific program direction and administration by

the Office of the Director, with assistance from

grant and contract science managers, finance,

human resources, legislation, science program

direction and assessment, and technology transfer

staff. The review and oversight activities of the

National Cancer Advisory Board and President’s

Cancer Panel also are included. This part of the

budget also supports a share of central NIH facilities and operations, and extramural program staff

salaries (intramural staff salaries and intramural

facilities maintenance are included under the

intramural research budget).
36 The Nation’s Investment in Cancer Research

Extraordinary Opportunities 

for Investment

Over the past thirty years, we have witnessed

dramatic changes in our fight against cancer.

The revolution in molecular biology, along

with the emergence of powerful new technologies,

have enabled us to gather an impressive body of

knowledge about cancer’s very nature. Today we are

able to identify many of the biochemical pathways

in a cell that become disrupted in cancer, and we

are gaining a fuller understanding about how such

changes contribute to a cancer cell’s abnormal and

dangerous behavior in the body. We also are gaining important insights into how the vulnerability of

DNA – our genetic material – and elements in our

environment and lifestyle interact to give rise to

this disease. For the many who struggle with cancer,

these striking changes in the science and technology of cancer research are reflected in marked

improvements in treatments and a heightened

chance for survival. They also are reflected in more

effective prevention, particularly for those who may

be at increased risk for the disease. These are

important advances, yet as long as people continue

to suffer from cancer, our work is not complete.

Three years ago, NCI acknowledged that to conquer cancer, we must choose a path that not only

maintains our pace of discovery but one that speeds

progress and optimizes our ability to overcome this

disease. This path is great science – science that is

anchored in exceptional quality, marked by vision,

imbued with imagination – a path that tenaciously

follows opportunities for discovery. In 1996, NCI

identified areas of extraordinary opportunity for

investment in cancer research. We defined areas of

discovery in which focused efforts and increased

resources could produce dramatic progress toward

reducing the burden of cancer. If pursued, these

extraordinary opportunities for investment – new

doors to discovery opened by past successes – would

provide profound insights into how cancer develops, paving the way for better techniques to prevent, detect, diagnose, and treat the disease. 

Four areas originally were chosen as investment

areas – Cancer Genetics, Preclinical Models of

Cancer, Imaging Technologies, and Defining the

Signatures of Cancer Cells. Since selecting these

areas in 1996, we have focused on putting into place

several dozen innovative projects – the Cancer

Genetics Network, the Mouse Models of Human

Cancers Consortium, In Vivo Cellular and Molecular

Imaging Centers, and the Cancer Genome Anatomy

Project (CGAP), to name a few – that provide the

infrastructure for basic discovery. Many of these projects are described in the following pages. 

This year, we intensively evaluated our current

direction and progress in each investment area to

chart a course for our second generation of efforts.

We determined that our primary focus for each of

these extraordinary opportunities should be to

move from process to product in the coming years –

to use the infrastructure established in each area to

resolve fundamental questions about cancer and

produce tangible improvements in cancer detection, diagnosis, and treatment. For example, our

charge now will be to take cancer genes identified

through CGAP and determine how they contribute

to cancer, how they can easily be detected in people

at risk, and how they can be targeted through new

treatments. From this evaluation, we also determined that we should broaden our Cancer Genetics

investment area to Genes and the Environment,

and integrate our efforts in Preclinical Models into

the other investment opportunities. 

We also identified three new areas of extraordinary opportunity for investment: Research on

Tobacco and Tobacco-Related Cancers, Cancer

Communications, and Molecular Targets of

Prevention and Treatment. As with the opportunities identified originally, each of these areas is
rife with possibilities for taking us to a new era in

cancer prevention and cancer care. 

An investment in each of these six areas promises to drive forward our understanding and control of cancer. 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 more importantly – will impair our ability to better care for

those whose lives have been touched by cancer. 

Extraordinary Opportunities 37

Opportunities

Cancer

Communications

11% Genes and the

Environment

17%

Cancer

Imaging

15%

Defining the

Signatures of 

Cancer Cells

23%

Molecular

Targets

17%

Research on

Tobacco

& Tobacco

Related

Cancers

17%

Selecting Extraordinary

Opportunities

I

n 1996, NCI, with formal input from over 60 cancer

scientists, educators, advocates, and community

leaders, identified four research areas of exceptional

promise in the cancer field – Cancer Genetics,

Preclinical Models of Cancer, Imaging Technologies,

and Defining the Signatures of Cancer Cells – and

pledged to focus increased attention and investment

on these areas for a three-year cycle.

In 1998, as this first cycle drew to a close, NCI

again approached scientific, professional, and lay

experts in the cancer field to revisit the “extraordinary

opportunities” and select emerging investment

research areas for the next three-year cycle. NCI

received over 250 responses from our grantees, members of our advisory boards, and advocacy groups. We

then assessed the responses, blended related meritorious ideas from the initial selected extraordinary opportunities, and selected three additional new investment

areas for a total of six – Genes and the Environment,

Cancer Imaging, Defining the Signatures of Cancer

Cells: Detection and Diagnosis, Molecular Targets of

Prevention and Treatment, Research on Tobacco and

Tobacco-Related Cancers, and Cancer Communications. 

These extraordinary opportunities are different from

the other important research areas supported by NCI;

they are areas where focused efforts and increased

resources could produce dramatic progress toward

reducing the burden of cancer. To qualify as extraordinary opportunities, these research initiatives must: 

■ Respond to important recent developments in 

knowledge and technology;

■ Offer approaches to cancer research beyond the size,

scope, and funding of our current research activities; 

■ Be implemented with specific, defined investments;

■ Be described in terms of achievable milestones, 

with clear consequences for not investing; and 

■ Promise advances for making progress against 

all cancers.

In addition, these investment areas will result in

new extramural grant or contract awards; collaborative

efforts with other institutes, government agencies, or

the private sector; and new or expanded scientific programs within NCI divisions. They promise to take us to

a new era in cancer prevention and care. 

Extraordinary Opportunities for

Investment Increase

(dollars in thousands)

Amount

Genes and the Environment $65,036

Cancer Imaging 58,700

Defining the Signatures of Cancer Cells 93,000

Molecular Targets 66,375

Research on Tobacco & Tobacco-Related Cancers 66,000

Cancer Communications 43,000

Total $392,111*

* $12,111 towards Investment areas included in Core budget level.
THE OPPORTUNITY

Dramatic scientific advances have led to new and

fundamental insights into the causes of cancer.

Fueled by conceptual and technical breakthroughs,

the often breathtaking pace of scientific discovery

has engendered a tremendous sense of optimism

among cancer researchers that new avenues will be

found to detect, treat, and prevent cancer. Nowhere

is this sense of promise greater or the potential

implications more profound than at the interface of

the fields of epidemiology and genetics. By marrying

the epidemiologic approach – study of the distribution and causes of cancer in human populations –

with cutting-edge genetic and related molecular

technologies, we will be able to:

■ Identify genes that predispose people to cancer

(cancer susceptibility genes) whose pathways of

action will point to previously unsuspected

environmental carcinogens, including those

related to lifestyle exposures.

■ Detect the slight to moderate elevations of risk

resulting from certain types of exposures by

studying genetically susceptible subgroups.

■ Design new approaches to diagnose, prevent,

and treat cancer based on an understanding of

how genes modify and interact with environmental exposures.

■ Quantify cancer risks associated with geneenvironment interactions, which will direct

individual and public health strategies aimed 

at preventing and controlling cancer. 

The importance of lifestyle and other environmental exposures as causes of cancer is unquestionable. The pivotal role of environment is

reflected in the substantial variation in cancer

incidence around the world, and in the changes 

in risk observed among groups that migrate and

become acculturated in the host country.

Furthermore, epidemiologic research has succeeded in identifying a wide range of cancer-causing

exposures, including tobacco use, dietary components, sunlight, ionizing radiation, environmental

chemicals, infectious agents, obesity, exercise, 

hormones, and reproductive factors. Nevertheless,

the causes of many cancers remain elusive. While

better approaches to measuring exposures will provide new insights, it is clear that the environment

represents only part of the equation in determining who will get cancer. It also is important to

understand cancer susceptibility. For example, why

does one person with a cancer-causing exposure

(such as smoking or infection with human papillomavirus) develop cancer, while another does not? 

Viewing such questions through the lens of

genetics promises to provide insights into these

apparent paradoxes. The scientific investment in

cancer genetics, initially focused on the intensive

study of rare cancer-prone families, already has paid

huge dividends. These studies have opened a

unique window into the basic mechanisms of cancer, with benefits extending well beyond the rare

families from which they were derived. This is

because the genes identified by these studies are

altered forms of normal genes involved in key biochemical chains of events (pathways) controlling

fundamental cell processes. It has become clear that

these same pathways contribute to the development

and progression of the more common, non-hereditary forms of cancer. Yet even among individuals

who have inherited cancer-predisposing genes, the

risk of developing cancer appears to be modified by

other genetic and environmental factors. There is

mounting evidence that one’s genetic make-up may

influence susceptibility or even resistance to cancercausing exposures. Opportunities now exist to

determine how variations in these genes combine

with environmental and other factors to induce

cancer in the general population. 

Three years ago, we identified cancer genetics

as an area of extraordinary opportunity. We recognized that to exploit fully this area’s potential – to

move it forward at the accelerated pace that accu1 Genes and the Environment

OPPORTUNITY

38 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 39

Opportunities

mulated knowledge and powerful technological

advances now permit – new initiatives were 

needed. Many of today’s new opportunities in the

area of genetics are a direct benefit of these scientific investments. For example, NCI’s Cancer

Genome Anatomy Project (CGAP) has resulted

in the discovery of approximately 30,000 new

genes. New technologies have permitted scientists

to determine which genes are expressed (active) in

normal and cancerous tissues. There has been an

exponential increase in the pace of identifying

genes that maintain the integrity of our genetic

material, regulate cell growth and development,

and determine our response to hormones and

other chemicals produced by the body as well as

environmental agents. Related discoveries have

enabled us to characterize the function of hundreds of new genes and pathways. Vast public data

bases contain millions of entries describing gene

sequences, their expression in different tissue

types, and their location in the human genome.

These advances are ushering in a new generation of epidemiologic research that will lead to a

comprehensive understanding of environmental

and genetic determinants of cancer. However, the

exciting opportunities of this emerging field –

referred to as “molecular epidemiology” – are

accompanied by enormous challenges. Population

studies sufficiently powerful to examine the complex interactions of multiple genetic and environmental factors will involve unprecedented numbers of participants and will require new research

infrastructures and strategies for interdisciplinary

collaboration. At the same time, we must strive to

ensure that individuals will be helped, not

harmed, by their knowledge of risk. What psychosocial, legal, ethical, and clinical issues will

arise from being able to determine cancer risk?

How can we help people to cope with the information and to take appropriate action? What will

be the impact on the individual, the family, and

the medical care system? These critical questions

must be addressed with the same urgency and dedication with which we pursue the scientific opportunities.

THE GOALS

■ Identify environmental causes of cancer using

new epidemiologic and genetic approaches.

■ Identify genes that modify (increase or

decrease) cancer risk, including the risk resulting from environmental exposures.

■ Integrate information on genetic susceptibility

and environmental exposures to estimate 

cancer risks for individuals, families, and 

populations.

■ Develop new strategies for cancer prevention,

early detection, and treatment, building upon

new knowledge about the genetic and environmental determinants of risk. 

THE PLAN

Objectives

1. Conduct large-scale studies of cancer in

human populations to identify new susceptibility genes, environmental risk factors, and

their interactions with one another.

■ Form a consortium of investigators directing

large, prospective cohort studies of the 

general population. 

■ Develop a network of cohorts totaling one

million individuals under active follow-up by

coordinating studies in which genetic and

exposure information is collected; add 

biologic specimen collections where needed.

Use this resource to study gene-environment

interactions for common cancers (e.g., breast,

prostate, lung, colon, and lymphoma), 

particularly those related to exposures that

are best studied prospectively (e.g., diet,

endogenous hormones).

■ Develop the infrastructure within existing

population-based cancer registries to conduct

a coordinated series of large-scale case-control studies that include biospecimens and indepth exposure data collection. Specifically:

– Collect biospecimens and detailed exposure

information on 12,000 cancer cases and

8,000 members of the general population in

the initial three years of this program. 
– Use this resource to study gene-environment interactions for cancers of intermediate or lower incidence (e.g., pancreas,

ovary, kidney, leukemia) and for studies of

the more common tumors that require

intensive assessment of exposures and 

biological markers.

– Give special attention to studies of tumors

with rising incidence and mortality rates,

racial and ethnic disparities, and unusual

geographic patterns. 

– As appropriate, integrate population-based

components of the Cancer Genetics

Network (CGN) and the Cooperative

Family Registries (CFRs).

■ Establish regional biospecimen repositories and

high throughput genotyping facilities to ensure

high quality, cost-efficient handling of biologic

samples from molecular epidemiology studies.

■ Form a network of resource laboratories to

develop and conduct specific laboratory tests

(e.g., hormonal, gene expression, immunological, nutritional, toxicological) on biologic

samples from various study populations.

■ Develop informatics systems that collect,

store, analyze, and integrate the vast amounts

of epidemiologic, clinical, and laboratory data

generated by large-scale studies, and safeguard

the confidentiality of all research data.

2. Develop new ways of assessing and 

measuring environmental exposures for 

use in population studies.

■ Develop new epidemiologic methods for assessing complex exposures over a lifetime (e.g., diet,

nutrition, occupational, and other environmental hazards), including computer-assisted interviewing techniques and improved data bases for

nutritional and environmental exposures.

■ Expand the NCI’s Unconventional

Innovation Program and other funding mechanisms to develop new techniques for using

very small amounts of biologic samples to

quantify exposures (e.g., pesticides, nutrients). 

■ Expand the Phased Innovation Award and

Small Business Innovation Research program

to develop non-invasive methods of collecting DNA for molecular studies (e.g., buccal

cells) and techniques to maximize the use of

small quantities of genetic material. 

■ Supplement ongoing research programs to

develop and validate measures of cumulative

cellular genetic and molecular exposure to environmental carcinogens in non-tumor tissue.

■ Expand and supplement research programs

including CGAP to develop and validate

molecular approaches to define in tumor cells

the characteristic mutation pattern of DNA

damage – the “molecular fingerprint” – that

implicates a specific carcinogen.

■ Use emerging technologies to develop molecular and immunologic techniques that will

enable screening of large numbers of biologic

samples to identify infectious agents relevant

to human cancer. 

■ Work with academic centers, including

schools of public health, to train highly

skilled scientists needed to carry out molecular epidemiology studies.

3. Identify and characterize gene variations

involved in key molecular pathways 

important in cancer.

■ Expand the CGAP programs to identify all

cancer-relevant genes and common variants.

As part of this effort:

– Increase the scope of gene discovery efforts

within the Tumor Gene Index (TGI); expand

the capacity of the Genetic Annotation

Initiative (GAI) infrastructure to delineate,

characterize, and validate gene variants.

– Recruit additional collaborators through

CGAP partnerships to accelerate GAI 

validation and confirmation efforts.

– Extend efforts to identify genetic variants

into clinically and epidemiologically

defined groups.

– Assess the relevance of gene variations in

the context of population studies of geneenvironment interactions.

■ Extend the GAI’s efforts to define key molecular pathways by increasing CGAP’s capacity

to assess gene expression profiles and by

establishing working groups to develop and

curate information on cancer genes and 

their related pathways.

■ Accelerate new technology development and

application by expanding the GAI

Technology Partners initiative and the

Unconventional Innovation Program.

40 The Nation’s Investment in Cancer Research
4. Develop new experimental models that 

parallel human cancer-related genes, 

pathways, and processes. 

■ Augment the Mouse Models of Human

Cancers Consortium (MMHCC) to derive

and refine mouse models of all known human

hereditary cancer genes.

■ Generate valid mouse models based on epidemiologic observations on genetic and environmental modifiers of cancer risk. Specifically:

– Support a GAI for the mouse in a 

systematic effort to identify common 

DNA-based genetic variants.

■ Augment the Web-based forum within the

MMHCC to integrate emerging knowledge

about cancer susceptibility from experimental

models and studies on human populations.

■ Support the MMHCC to discover mouse

genes that modify cancer susceptibility to

illuminate cancer pathways in humans. 

– Augment MMHCC repository support to

derive and distribute consomic and recombinant inbred congenic mouse strains.

– Use susceptible mouse models to evaluate

environmental factors for their potential to

modify cancer development.

– Use mouse cancer models to discover biomarkers and in vivo approaches for early

detection and to develop and test new 

prevention strategies.

■ Develop and use non-mammalian organisms

as models of complex interactions among the

pathways and processes that contribute to

cancer etiology.

5. Identify and characterize cancer-predisposing

genes in high-risk families and investigate

how the expression of these genes is modified

by other genetic and environmental factors.

■ Enhance high-risk family recruitment

through mechanisms such as the CGN,

CFRs, cancer centers, and cooperative

groups. In addition, develop common

research tools such as family history instruments, model informed consent documents,

and research data protection standards;

expand mechanisms (e.g., Internet) to aid

family identification and referral into

research programs.

■ Use these resources to initiate large collaborative interdisciplinary studies of high-risk

families to quantify cancer risk among carriers

of identified major genes (e.g., BRCA1,

BRCA2, APC, VHL) and to investigate

genetic and environmental modifiers of risk.

■ Foster consortia of investigators to identify the

genetic basis for specific familial aggregations of

cancers that have not yet been linked to genes. 

■ Expand the capability and use of the NIH

Center for Inherited Disease Research

(CIDR) and other resources to accelerate

familial cancer gene identification.

6. Develop risk assessment models that integrate

information on genetic and environmental

determinants of cancer.

■ Augment selected population-based studies

and clinical trials to design and validate statistical models that predict individual cancer risk

for specific cancers. Develop strategies to communicate the resulting information to both

health professionals and high-risk persons.

■ Use these models to identify high-risk 

individuals for diagnostic, preventive, or 

therapeutic interventions. 

■ Develop statistical methods and models to

assess the population’s cancer burden that is

attributable to susceptibility genes, specific

exposures, and their interactions.

■ Use these population burden models to

inform public policy.

■ Use new and existing NCI initiatives, including transition career development and established investigator awards, to train investigators in clinical and population risk assessment

methodologies.

7. Enroll high-risk individuals into clinical 

protocols, and conduct studies to address 

the clinical, behavioral, and societal issues

associated with cancer susceptibility.

■ Through the CGN, CFRs, cancer centers,

and cooperative groups, recruit high-risk individuals into clinical studies to assess diagnostic and preventive interventions (e.g., the use

of innovative breast imaging strategies or preventive agents among BRCA1/2 carriers).

Extraordinary Opportunities 41

Opportunities
42 The Nation’s Investment in Cancer Research

■ Expand and extend selected NCI-supported

therapy trials to enable long-term follow-up

of survivors for late treatment effects, particularly risk of second cancers. Include biospecimen collections to evaluate the role of genetic susceptibility and other mechanisms of

cancer development.

■ Through the NCI Biobehavioral Research

Program, the CGN, CFRs, interagency collaborations, and other mechanisms, conduct

research into the genetics of specific behavioral traits related to cancer risk (e.g., smoking initiation and cessation).

■ Supplement existing genetic screening programs and other consortia to conduct behavioral research to assess the impact of predictive genetic testing and cancer risk assessment on high-risk individuals and their families, and to develop interventions for coping

with the implications of genetic information.

■ Develop and employ model procedures to

protect the confidentiality of participants in

NCI-sponsored research, and prevent disclosure of identifying information. Implement

recommendations from the Fall 1999 NCI

Conference on Confidentiality, Data

Security, and Cancer Research.

PROGRESS IN PURSUIT OF 

OUR GOALS

NCI has initiated a broad range of projects that

are providing many new opportunities for

studying genetic and environmental determinants

of cancer. Recent progress in several efforts is

highlighted below.

■ NCI launched the Cancer Genetics Network,

a collaborative multicenter infrastructure that

will study the genetic basis of cancer susceptibility and clinical outcomes; apply new genetic

information in medical practice; and address

psychosocial, ethical, legal, and public health

issues. In addition, NCI established the

Cooperative Family Registries for breast/ovarian and colon cancer to foster interdisciplinary

research in the genetic epidemiology of these

cancers. 

■ The Genetic Annotation Initiative (GAI), 

part of the Cancer Genome Anatomy Project

(CGAP), has been established to expand the

array of tools available for genetic analysis. The

GAI identifies variations in genes discovered

through the CGAP. Over 10,000 gene variations have been discovered and in June 1999,

NCI made this information available on a pubT he year is 2000. Due largely to sun exposure, one in

75 people can expect during his or her lifetime to

develop a disfiguring and potentially deadly cancer of

the skin, mucous membranes, eyes, and central nervous

system – malignant melanoma. In the United States,

cases of melanoma have more than doubled since 1970,

and the incidence of this disease is increasing dramatically in persons with light-colored skin in all parts 

of the world. 

Unaware of the danger, people who were sun-worshippers

in their teens and early 20s, and people doing outdoor

work without sun protection, are now, at 40 or 50 years

of age facing the consequences of irreparable DNA damage

the sun's ultraviolet light has caused in their skin. 

Unlike basal cell and squamous cell carcinomas, common

skin cancers that typically can be removed surgically and

require no further treatment, malignant melanoma is 

SPOTLIGHT ON RESEARCH

Malignant Melanoma

5

10

15

20

1973 1976 1979 1982 1985 1988 1991 1994 1996

Year

Incidence

Whites

Blacks

Melanoma Incidence 1973-1996

Blacks and Whites (per 100,000 people)
Extraordinary Opportunities 43

Opportunities

lic Web site for investigators to validate and use. 

■ The Cancer Chromosome Aberration Project,

also part of CGAP, has developed tools for

characterizing in detail the distinct chromosomal alterations associated with cellular transformation to malignancy. Studies recently funded

include a repository of bacterial artificial chromosomes (BACs) mapped at high resolution

across the human genome.

■ This year, NCI funded the development of a prototype geographic information system (GIS) for breast cancer

studies. The GIS will use existing data

bases from Federal, state, and local government and private sources to integrate environmental data on drinking

water contaminants, ambient air pollution, electromagnetic fields, ionizing

radiation, pesticides, and other toxic

chemicals. The system will be piloted

as part of the Long Island Breast

Cancer Study. 

■ This year, NCI funded the Mouse

Models of Human Cancers Consortium, a 

program designed to develop and refine experimental models that reflect the etiology and 

progression of human cancer. These models 

will accelerate the discovery of genes that 

modify susceptibility to cancer and permit the

design and testing of new approaches for 

prevention, early detection, and treatment.

■ Under the auspices of the Mouse Cancer

Genome Anatomy Project (MCGAP), studies

are underway to investigate molecular determinants of cancer in the mouse for comparative

studies in human tumors. NCI will make the

MCGAP reagents publicly available in

support of efforts to identify mouse modifier genes involved in cancer etiology.

■ The success of research in cancer 

epidemiology and genetics depends

critically on our ability to safeguard

the confidentiality of genetic and

other sensitive information collected

in research studies. NCI is calling for 

a national discussion engaging the 

scientific, bioethics, and advocacy

communities to address these issues,

which have profound implications for

the conduct of future research. To

stimulate public discourse, NCI has

developed a “white paper” on confidentiality, data security, and cancer

research. 

invasive – and therefore quite serious – even if it only

penetrates the skin to a depth of less than a single millimeter. Many patients whose melanoma has not penetrated into surrounding tissue can be cured by surgery alone.

For those with more advanced melanoma, new and emerging treatments hold promise for arresting the progress 

of the disease, or even curing it.

Drugs that enhance the immune system's response to tumor

cells and drugs that attack the tumor cells are being studied in patients with high-risk and metastatic melanomas.

One such treatment, high-dose interferon alpha-2a, has

been approved by the Food and Drug Administration for

treatment following surgery for melanoma patients who are

at high risk of disease recurrence.

In addition, NCI is researching new approaches to cancer

treatment vaccines. In the vast arsenal of the human

immune system, there are special white blood cells that

can infiltrate tumors, and scientists have identified within

these cells specific molecules involved in cancer rejection.

Researchers are now able to take a melanoma patient’s

own tumor infiltrating white blood cells, grow or “amplify” the cells, their associated genes, or gene products,

and use them to treat the cancer. This individualized therapy, alone and in combination with the immune response

modifier interleukin-2, has shown promising results in initial studies in patients with metastatic melanoma. Other

early studies suggest that similar new immunologic

approaches will prove useful not only in treating

melanomas, but in treating certain groups of patients

with breast cancer, colon cancer, ovarian cancer, and lymphomas. Such treatment, called immunotherapy, may lead

to a major advance in our progress against the family of

persistent and deadly diseases known as cancer.

To find out 

more about 

confidentiality

issues, visit

http://www.

nci.nih.gov/

confidentiality.

html
44 The Nation’s Investment in Cancer Research

Conduct population-based studies of gene-environment interactions. $20.0 M

■ Create a network to coordinate prospective studies involving a total of one million participants.

■ Develop infrastructure for case-control studies initially involving 20,000 participants.

■ Develop repository, laboratory, and informatics infrastructures.

Assess and measure environmental exposures for use in population studies. $8.0 M

■ Develop epidemiologic methods to assess complex exposures.

■ Develop non-invasive DNA collection methods and technologies.

■ Develop molecular measures of cumulative exposure to environmental carcinogens 

in non-tumor tissue.

■ Develop and validate molecular approaches to define molecular fingerprints in tumor cells 

that implicate specific carcinogens.

■ Develop immunologic and genotypic approaches to identify infectious agents in human cancers.

■ Support interdisciplinary training programs in molecular epidemiology.

Identify and characterize gene variants in key molecular pathways. $5.0 M

■ Expand CGAP programs to identify, characterize, and validate gene variants relevant to cancer.

■ Extend efforts to identify cancer-related molecular pathways.

■ Accelerate new technology development and application.

Develop animal/experimental model systems. $5.0 M

■ Develop mouse models of human cancer-related genes.

■ Develop organisms as models of gene-gene and gene-environment interactions.

Conduct family-based studies. $10.0 M

■ Enhance recruitment of high-risk families into research studies.

■ Initiate large collaborative studies to quantify cancer risk and to investigate genetic and 

environmental modifiers of risk.

■ Support consortia to study familial clusters of cancers not yet linked to genes.

■ Support use of CIDR and other resources to identify familial cancer genes.

Develop risk assessment models. $2.0 M

■ Develop population-based and clinical studies to design and validate risk assessment models.

■ Develop methodologic approaches incorporating genetic and environmental determinants.

■ Train investigators in clinical and population risk assessment methodologies.

Expand clinical research. $12.0 M

■ Recruit high-risk individuals into studies assessing diagnostic or preventive interventions.

■ Evaluate late effects of cancer treatment, including gene-environment interactions.

■ Conduct research into the genetics of specific behavioral traits related to cancer risk.

■ Assess the impact of predictive genetic testing and cancer risk assessment on high-risk 

individuals and their families; develop interventions for coping with genetic information.

■ Develop procedures to protect participant confidentiality.

Management and support. $3.0 M

TOTAL $65.0 M

Resources: Genes and the Environment
Extraordinary Opportunities 45

Opportunities

OPPORTUNITY

THE OPPORTUNITY 

As recently as 25 years ago, a physician or surgeon who suspected the presence of a tumor in

a patient had few options. Order x-ray studies to

define and localize the tumor as accurately as the

pictures would permit. Schedule the patient for

surgery and examine the tumor directly, excise a

portion of the unhealthy tissue for biopsy, remove

the tumor if possible, and explore surrounding tissues to determine whether the cancer had spread. 

Over the last quarter century, refinements in

imaging technology have substantially broadened

the range of medical options. Current imaging

tests now provide much clearer and more detailed

pictures of organs and tissues than were possible

previously. Imaging already has had a lifesaving

effect in detecting some early cancers. X-ray mammography, for example, has saved the lives of

many women by revealing the presence of very

small cancers before they could be detected by

physical examination. Computed tomography

(CT) and ultrasound permit physicians to guide

long, thin needles deep within the body to biopsy

organs, often eliminating the need for an open

surgical procedure. CT can reveal whether a

tumor has invaded vital tissue, grown around

blood vessels, or spread to distant organs; important information that can help guide treatment

choices. 

But the power of imaging technology allows us

to do more than simply view structures anatomically, such as visualizing bones, organs, and tumors

in the body. Functional imaging – the visualization of physiological, cellular, or molecular

processes in living tissue – allows us to see such

things as blood flow, oxygen consumption, or glucose metabolism in real time, as they take place in

living cells of the body. As we gain a better understanding of the fundamental nature of cancer, cellular and molecular imaging will be a key tool in

translating this knowledge into better ways of

diagnosing, treating, and preventing the disease.

Imaging can identify the kinds of molecular structures/receptors that cover the surface of a tumor,

information that potentially can predict how it

may behave and respond to certain treatments. 

Or, by providing a picture of glucose utilization in

tumor cells, imaging can demonstrate – without

the need for a biopsy – how a tumor is responding

to a recently administered treatment. 

And seeing how the processes and pathways

inside a cell change as the cell transforms from

normal to cancerous will allow us to detect this

change in people earlier in the cancer process,

perhaps before a tumor has even had the chance

to become fully malignant. Eventually we expect

to be able to visualize the actual molecular signatures of a cancer. We will be able to tell, in the

radiology suite of a hospital, which genes are being

expressed in a person’s cancer, and we will be able

to translate this information directly into better

management of the disease. In other words, the

ability to detect, through imaging, the molecular

changes associated with a tumor cell will vastly

improve our ability to detect and stage tumors,

select appropriate treatments, monitor the effectiveness of a treatment, and determine prognosis. 

The potential of imaging to improve cancer

treatment extends well beyond using imaging

information to help select effective treatments or

preventives. For example, combining precise 

imaging techniques with radiation sources and

high performance computing is significantly

improving our ability to shape radiation treatments to the tumor’s three-dimensional contours.

In principle, imaging techniques can be interfaced

with other tumor-killing approaches – toxic chemicals, gene therapy, heat, and cold – to more precisely guide tissue destruction at the tumor site.

Being able to distinguish between cancerous and

normal tissue and deliver treatments only to diseased tissues in a minimally invasive way will

potentially minimize surgical trauma, shorten

Cancer Imaging 2
46 The Nation’s Investment in Cancer Research

recovery time, and reduce health costs. 

Parallel developments in image enhancement

agents are improving our ability to capture

changes in the biochemical makeup of cells and

other living structures. Enhancement agents contribute to image formation in three ways. They

may localize in certain body organs or structures

(anatomic localization); they may attach to specific molecules in the body (receptor localization); or

they may become activated by certain biochemical

or physical conditions, such as the presence of a

specific enzyme or low oxygen concentration in

the cell (activatable agents). We anticipate that

contrast agents of the future will be able to reveal

the functional characteristics of tumors that determine clinical behavior and response to therapy. 

In imaging, as elsewhere in cancer research,

animal models of cancer will make possible certain

kinds of studies that are difficult or impossible to

perform in people. In addition to learning more

about cancer, work with animal models can enable

imaging technology improvements that then can

be applied in the clinic. Imaging permits repetitive

observations of the biological processes underlying

cancer growth and development, and the level of

resolution with some imaging modalities is now

approaching the size of individual cells. Imaging

also can help assess the effectiveness of new

instruments, and animal studies will be crucial in

developing a new generation of clinically useful

imaging agents to assess drug effects in patients. 

Although it seems clear that better imaging

tools will improve patient care, we need better

ways of measuring that improvement. In evaluating new therapies, a cure or prolonging the

patient’s life are often important measures of effectiveness. For diagnostics, however, these measures

are relatively insensitive. The problem is that 

survival is a global reflection of all diagnostic and

therapeutic interventions that a patient experiences; it often is difficult or impossible to ascribe

improvements in survival to a particular diagnostic

test. More appropriate measures of effectiveness

might include, for example, greater efficiency of

testing, less cost, fewer hospital days, less morbidity, and the need for less extensive or disfiguring

treatment. In short, we need improved methodologies to assess the ultimate value of diagnostic tests. 

Three years ago, NCI recognized the great

untapped potential that imaging technology holds

for cancer and identified it as an area of extraordinary opportunity. With this designation, we began

a three-year effort aimed at significantly advancing

imaging to more fully exploit its promise for cancer research and care. By establishing an Imaging

Working Group, we stimulated constructive communication among experts from diverse disciplines

who have advised NCI about how we can quickly

and effectively move imaging research forward.

The efforts of this group helped us define research

needs and opportunities. In the past year, we

launched a national network to evaluate diagnostic imaging technologies. We also have established

several small-animal imaging research centers. 

Still, we have much important work to do

before the full promise of the imaging sciences is

realized for cancer. Having laid the groundwork,

we now will target tangible improvements in cancer detection, diagnosis, and treatment – results

that will provide real clinical benefits for people

with cancer and those at risk. 

THE GOALS

■ Develop and validate imaging technologies and

agents (e.g., probes, radiocontrast agents) that

have the sensitivity to detect precancerous

abnormalities and very small cancers.

■ Develop imaging techniques that identify the

biological properties of precancerous or cancerous cells that will predict clinical course and

response to interventions.

■ Develop minimally invasive imaging technologies that can be used in interventions and in

assessing treatment outcomes. 

■ Foster interaction and collaboration among

imaging scientists and basic biologists, chemists,

and physicists to help to advance imaging

research. 

■ Create infrastructures to advance research in

developing, assessing, and validating new 

imaging tools, techniques, and assessment

methodologies. 
THE PLAN

Objectives

1. Accelerate development of clinically useful

technologies for detecting malignant and 

precancerous cells and for visualizing their

functional characteristics.

■ Expand the number of In Vivo Cellular and

Molecular Imaging Centers. (See Progress

section for description) 

■ Expand the Small Animal Imaging Resources

Program to improve access to researchers testing new approaches to diagnosis, treatment,

and prevention in animal models of cancer.

NCI will foster collaborations between this

program and the Mouse Models of Human

Cancers Consortium. 

■ Support multidisciplinary centers of expertise

to develop optical technologies and perform

clinical feasibility tests of instruments able to

visualize epithelial tissue at risk for common

cancers and recognize the optical signatures

of precancerous abnormalities. 

2. Develop, synthesize, validate, and 

distribute to the research community 

novel imaging agents. 

■ Create a program similar to NCI’s Rapid

Access to Intervention Development initiative (designed to accelerate the movement of

novel interventions from the laboratory to

the clinic) for imaging agents. NCI will, on a

competitive basis, synthesize, test, and distribute probes that image the physiological

and functional status of tumor tissue in the

human body.

■ Establish a publicly available data base of

agents available to the research community,

together with information on their properties. 

3. Expand and improve clinical studies of 

imaging modalities and image-guided 

interventions.

■ Establish centers for developing and clinical

feasibility testing of technologies enabling

minimally invasive, image-guided therapy for

localized malignancies (e.g., brain, breast,

prostate). 

■ Enable collaborations between the clinical

cooperative groups and the Diagnostic

Imaging Network (see Progress section for

description) for definitive testing of minimally invasive, image-guided interventions that

appear promising in early feasibility studies.

■ Expand the Diagnostic Imaging Network to

permit it to develop a full menu of clinical

trials relating to all major cancers. 

■ Develop methodologies to assess the medical

value of diagnostic tests in clinical trials.

Support the full development of outcomes

research as applied to the evaluation of imaging diagnostics. 

4. Integrate molecular and functional imaging

technologies into drug development and early

clinical trials. 

■ Support the development of in vivo and 

clinical imaging research tools for assessing

the biologic effect of cancer drugs on their

intended target or pathway. (See Molecular

Targets)

5. Establish information archives and repositories needed by the research community. 

■ Establish data banks of standardized digital

images associated with known clinical 

outcomes.

■ Provide resources to develop and test image

processing and analysis algorithms on these

standardized data sets.

6. Provide innovative imaging equipment to the

research community for limited scale 

feasibility testing.

■ Establish a competitive program in which

innovative equipment prototypes developed

in industry or academia will be provided to

selected academic institutions for feasibility

testing, in close collaboration with the 

developer. 

PROGRESS IN PURSUIT OF 

OUR GOALS

Over the past year, NCI launched several exciting new initiatives and achieved important

progress in ongoing programs. The following

describes some of our new programs and activities

as well as the progress made in programs already

underway. 

■ Advances in both structural and functional

imaging technologies have produced remarkable tools for understanding, detecting, and

diagnosing cancer. Yet the power of these tools

Extraordinary Opportunities 47

Opportunities
could be amplified appreciably if advances in

imaging technology could be merged with the

myriad new discoveries in cancer-related genes

and proteins. A scientific gulf still exists

between basic scientists who discover new cancer genes and intracellular pathways – any of

which could serve as a diagnostic or therapeutic

target – and imaging scientists who focus on

non-invasive approaches to transform these discoveries into a greater understanding of cancer.

To narrow this gap, NCI will award two to

three grants in the coming year to support 

In Vivo Cellular and Molecular Imaging

Centers (ICMICs). ICMICs will facilitate

interaction among scientists from a variety of

fields to conduct multidisciplinary research on

cellular and molecular imaging. Because the

integration of this breadth of expertise is still in

its early stages, the NCI also will award six preICMIC planning grants. The pre-ICMIC planning grants will provide time and funds for

investigators and institutions to prepare themselves, organizationally and scientifically, to

establish an ICMIC.

■ Digital mammography is considered one of 

the most promising technologies for use in

large- scale screening programs to improve 

early breast cancer detection. To advance 

the state-of-the art in digital mammography

displays and workstation design, NCI has set

aside funds to encourage studies that focus on

research and development in critical areas to

make digital mammography a more useful

device in clinical settings.

■ Small animal models, particularly genetically

engineered mice, are powerful discovery tools,

but we have yet to capitalize fully on their

potential in cancer research. NCI will fund four

to five Small Animal Imaging Resource

Programs this year. This initiative will support

activities to develop and apply a wide variety of

imaging modalities that focus on functional,

quantitative imaging. Quantitating image data

for small animals will lead the way to quantitative methods that can be applied in humans.

■ Preclinical models of human cancer can be

valuable tools for developing and testing new

therapeutic, preventive, early detection, and

diagnostic imaging strategies. NCI will develop

and use a Preclinical Models Imaging Forum

(a mechanism that will include meetings and a

Web site) to link the expertise of participants

in the Mouse Models of Human Cancer

Consortium, imaging technique developers and

users of the small animal imaging centers, the

Diagnostic Imaging Network, investigators

using imaging techniques to observe patients,

and investigators who use model systems other

than mice. The information generated through

this forum will be helpful for designing and

testing imaging techniques to detect human

cancers and in developing and validating new

48 The Nation’s Investment in Cancer Research

SPOTLIGHT ON RESEARCH

How Can Spiral CT Improve Early Detection 

of Lung Cancers?

Finding lung cancers early is believed to be a missing

key to combating this deadly disease – the leading

cause of cancer death for men and women in the United

States. Yet despite intensive research, a reliable screening technique for early detection of lung cancers has

eluded discovery. Now, however, advances in imaging

technology have led to the development of a screening

technique, spiral computerized tomography (spiral CT),

that may prove to be the first screening method to 

find some of these cancers early and reduce lung 

cancer deaths. 

With spiral CT, the entire lungs, from the neck to the

diaphragm, can be scanned in less than 20 seconds – a

single breath-hold. Rapid scanning improves the detection

of smaller lesions since they are not moving in and out of

the field of view due to breathing; moreover, rapid scanning minimizes radiation exposure. Preliminary studies of

spiral CT have shown promise in detecting small cancers.

For example, adenocarcinomas, the most common lung

cancer, can be detected more readily with spiral CT than

with standard chest x-ray. However, this technology may

be less useful for detecting central airway tumors, such as 
preclinical models.

■ Before new or refined imaging tools can be used

as cancer diagnostic instruments, they must be

evaluated for their safety and effectiveness. In

March 1999, NCI funded the Diagnostic

Imaging Network to bring together imaging

experts from around the Nation to perform a

broad spectrum of multi-institutional clinical

trials on diagnostic imaging tools related to cancer. The Diagnostic Imaging

Network will establish collaborations

with NCI Cooperative Groups to expedite the integration of diagnostic imaging technologies into clinical trials

aimed at assessing new therapies. 

■ Improved imaging techniques can

enable clinicians treating prostate cancer to accurately localize and stage a

tumor, information that can be useful

for choosing treatments. NCI has set

aside funding to launch a new initiative aimed at developing non-invasive imaging

technologies for the localization, biopsy, and

minimally invasive treatment of prostate cancer.

■ New drug discovery programs are producing an

ever increasing number of molecules for investigation, in turn stimulating a need for research

that integrates imaging techniques into preclinical and clinical studies to assess newly developed therapeutic agents. NCI has set aside funding

for the development and application of labeled

therapeutic agents as compounds for imaging

studies and imaging agents that serve as metabolic markers of response to newly developed therapeutic agents.

■ NCI, the National Electrical Manufacturers

Association, the FDA, and the Health Care

Financing Administration are collaborating to develop partnerships with the 

imaging industry.

■ To stimulate the discovery, development, and advancement of highly

innovative new areas of imaging science, NCI has made available

Exploratory/Development Grants for

Diagnostic Cancer Imaging. These

grants are designed to provide investigators with the initial resources

required to accomplish feasibility and

pilot testing of innovative ideas. Some

of these feasibility studies will help 

generate new research programs in previously

unexplored areas. This ongoing program already

has been used to fund studies in a wide variety

of imaging areas, including new MRI technology to diagnose head tumors, and a system

employing both MRI and ultrasound in 

minimally invasive detection of prostate 

abnormalities.

Extraordinary Opportunities 49

Opportunities

squamous cell carcinomas, and very rapidly growing carcinomas, such as small cell lung cancers.

NCI is funding clinical trials to determine the size and

types of abnormalities that can be detected by spiral CT.

But many lesions detected with this technology may not

be malignant. Therefore, to avoid invasive, potentially

dangerous biopsy procedures such as open lung surgery,

we must consider carefully how we will evaluate the

abnormalities found with spiral CT. Two technologies are

available to aid in diagnosis: high-resolution CT, which

helps to distinguish between cancerous and non-cancerous tissue, and positron-emission tomography (PET),

which shows the differing uptake of radioactive isotope

“tracers” in benign growths and malignant tumors. 

Other diagnostic techniques are being studied. But the

potential physical and psychological complications arising

from evaluation of what eventually is found to be benign

disease must be recognized and addressed. NCI will also

fund studies to assess the benefits and risks of routine

lung cancer screening. 

For information

on the

Diagnostic

Imaging 

Network visit

http://www.

acrin.org
50 The Nation’s Investment in Cancer Research

Resources: Cancer Imaging 

Develop clinically useful technologies for detecting malignant and 

precancerous cells. $27.2 M

■ Fund 2 Centers and 8 four-year planning grants for In Vivo Cellular and Molecular Imaging

Centers. 

■ Support 10 additional Small Animal Imaging Resource Programs.

■ Support 4 multidisciplinary Centers of Excellence for Optical Technologies. 

Develop, synthesize, validate, and distribute novel imaging agents. $4.0 M

■ Create a RAID-like program for imaging agents – fund 3 to 6 agents.

■ Establish a publicly available data base of agents.

Conduct clinical trials of imaging modalities and image-guided interventions. $16.5 M

■ Establish 4 centers for development and clinical feasibility testing of image-guided therapy 

for localized malignancies.

■ Support collaborations between clinical cooperative groups and the Diagnostic Imaging Network.

■ Expand the Diagnostic Imaging Network.

■ Develop methodologies to assess medical value of diagnostic tests in clinical trials.

Integrate molecular and functional imaging technologies into drug development. $.0 M

(Budgeted in the Molecular Targets Opportunity.)

■ Support development of in vivo and clinical imaging research tools for assessing drug effects 

on intended targets.

Develop information archives and repositories. $1.5 M

■ Establish data banks of standardized digital images associated with known clinical outcomes.

■ Develop and test image processing and analysis algorithms on standardized data sets.

Evaluate innovative imaging equipment. $7.5 M

■ Establish a competitive program for feasibility testing of innovative prototypes.

Management and support. $2.0 M

TOTAL $58.7 M
THE OPPORTUNITY

I

n the 19th century, the light microscope

opened a new frontier in the study of disease 

by opening a window on the inner workings of the

cell. The science of pathology – the branch of

medicine that deals with the essential nature of

disease – expanded to include the study of structural changes in cells. For the first time, disease

could be linked to visible, recognizable changes 

in the cells of the body. 

At the cusp of the 21st century, new molecularbased technologies are bringing us to a similar

epiphany. These new technologies are enabling us

to identify features of individual cells in ways

unimagined by our 19th century predecessors. For

example, all cell types, depending on their functions, have unique, identifiable “signatures” – special characteristics such as which genes are active

and what proteins or other cellular products are

manufactured by the cell. Our new technologies

are enabling us to read and understand those signatures. We have learned that during the transformation of a normal cell to a cancer cell, the signature changes, and that change becomes a signal of

the presence of cancer. 

Further, we have learned that cells surrounding

the incipient tumor may also undergo changes

indicating that cancer is present. For example,

tobacco-induced molecular changes in the mouth

may predict the risk of developing lung cancer,

and cancers of the urinary tract may be signaled by

cancer cells that are “shed” in the urine. Reading

the signatures of these easily accessed cells may

enable us to develop simple, non-invasive tests to

find cancers located deep within the body. 

The implications of these findings are profound.

By reading cellular signatures accurately, we may

be able to detect and diagnose cancers before they

have had a chance to invade nearby tissues. In

fact, with the tools we are developing, a single

drop of blood from a patient’s finger may be all

that is needed to find a cancer, assess the threat it

poses by comparing its traits to profiles in an online library of tumor characteristics, choose the

best possible treatment, and monitor the patient’s

recovery. By assessing the meaning of individual

changes in the cell’s signature, we will be able to

determine which cancers are most likely to

progress and which are less likely to do so – a

dilemma that confronts, for example, doctors

treating patients with prostate cancer – thereby

avoiding the consequences of unnecessary treatment. By studying the sequence of changes a cell

undergoes as it transforms from normal to cancerous, we will gain important insights into the etiology of the disease. And by applying what we have

learned, we will be able to identify new targets, at

the molecular level, for effective prevention and

treatment. (For more on this exciting area of

scientific opportunity, see page 57.)

“Defining the Signatures of Cancer Cells” was

first identified as an area of extraordinary scientific

opportunity in 1996, and it continues to be an

area rich in scientific promise today. For example,

we now are in a position to learn new ways to

characterize tumors more efficiently – that is, to

determine which genes are active and inactive,

and the levels of specific proteins that are present

in a particular tumor. Such “molecular fingerprinting” will greatly enhance the specificity of cancer

diagnosis by allowing us to differentiate among

tumors at the molecular level, and will enable us

to devise treatments targeted at cellular subtypes

of different cancers. We can now use changes in

molecular signatures to help us identify infectious

and environmental agents that may be responsible

for the development or progression of a tumor. In

addition, while many of our previous efforts have

centered on identifying genes involved in cancer,

we are very interested in learning more about the

functions of the proteins produced by these genes.

Finally, there has been a gap between the identification of preclinical tumor changes, early evaluaDefining the Signatures of Cancer Cells: 

Detection and Diagnosis

3 OPPORTUNITY

Extraordinary Opportunities 51

Opportunities
tion of new identification techniques, and their

clinical application. We now have the opportunity

to synthesize these disparate findings into a body

of knowledge that will translate into real health

benefits. Our ultimate goal is to push back the

detection and diagnosis of cancer to the earliest

stages, thereby offering the potential to focus

intervention efforts at preventing overt disease,

rather than at treatment.

Clearly, we have made substantial progress.

However, much remains to be done if we are to

take full advantage of the opportunities in this

area. The diagnostic value of molecular-based

methods must be confirmed and their practical

benefits established against the background of

conventional medicine. New technologies must be

developed, and new preclinical models must be

created and validated to establish our findings.

Finally, it is crucial that we develop the sophisticated computer systems, data bases, and statistical

methods needed to integrate the complex information being generated by the new technologies with

the biologically relevant data. In this way we will

be able to validate the predictive value of the new

approaches. 

THE GOALS

■ Complete the molecular catalogue of cancer by

characterizing the molecular profiles of precancerous and cancer cells at all stages of clinical

disease, associated host cells, and surrounding

tissue and body fluids.

■ Develop improved methods for detecting precancerous lesions and cancers at their earliest

stages, when cure is most possible.

■ Develop a new taxonomy for cancer based on

the molecular signatures of cells and use it to

develop improved strategies for cancer diagnosis

and prognosis.

■ Develop preclinical models that reflect the

molecular basis of human cancer etiology and

progression; use the models to inform the

design of new molecularly based approaches for

early detection, diagnosis, prognosis, and treatment of cancer, and to test and refine these

approaches.

■ Develop integrated technologies to detect

defined molecular signatures that predict cancer

occurrence or progression and provide a seamless interface with intervention.

THE PLAN

Objectives

1. Continue to characterize the molecular profiles of precancerous and cancer cells at all

stages of clinical disease, associated host cells,

and surrounding tissue and body fluids. 

■ Complete the Tumor Gene Index of genes

expressed in cells at all stages of tumor 

development.

■ Enhance the Director’s Challenge to establish

molecular profiles of human cancer and

develop molecular classification schemes for

all human cancers.

■ Fund the development of data bases and analytic tools for comprehensive molecular

analysis.

2. Establish and make available tissue resources

to maximize the practical application of

molecular signatures to problems in cancer. 

■ Establish a national tissue resources system

for all major cancers, including cancers of the

lung, breast, prostate, colon, head and neck,

brain, soft tissue, blood, bone, the gynecologic and genitourinary systems, and childhood

malignancies.

■ Develop tissue arrays and implement a system

for distributing tissue and tumors.

■ Publicize the existence and capabilities of tissue resources to the research community.

■ Partner with the advocacy community to 

develop a public education program on issues 

surrounding tissue donation for research.

3. Develop and deploy a robust informatics 

system for molecular pathology.

■ Establish pathology standardization and

agreement on common data elements.

■ Develop query and search capability for the

national tissue repositories.

■ Provide automatic encryption features for

personal identifiers associated with tissue

resources.

52 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 53

Opportunities

■ Establish linkages to population data bases,

such as SEER and other registries, to aid in

acquiring outcome and follow-up information.

4. Create a classification system for cancer and

pre-cancer based on the molecular signatures

of cells; use it to model improved approaches

to early detection, diagnosis, and prognosis.

■ Initiate a “Director’s Challenge” to fund 

consortia to identify molecular signatures 

of preneoplastic lesions associated with 

cancer development.

■ Fund the development of tissue repositories 

of precancerous lesions.

■ Support the development of standards for

correlating molecular and pathologic criteria

used to define stages of human cancer 

development.

■ Expand the Early Detection Research

Network to expedite the discovery, validation, and development of new early detection

tests for all major human cancers.

■ Support the development of high throughput

technologies for isolating and enriching cells

shed in body fluids.

■ Support the development of high throughput

assays for the molecular characterization of

proteins and for detecting informative markers in body fluids.

5. Validate molecular signatures for their potential value in cancer diagnosis and prognosis,

and in predicting intervention response.

■ Create a Diagnostics Validation Network to

provide the research community with a

means to evaluate and validate signatures

with possible diagnostic value. Establish linkage to clinical information (i.e., pathology,

histology, treatment response, stage, and

grade) to establish surrogate molecular endpoints for application in cancer prevention

and treatment studies.

■ Provide supplemental funding to groups 

conducting prevention and therapy studies 

to evaluate biomarkers for their ability to 

predict response to therapeutic and prevention interventions.

6. Develop preclinical models that reflect the

genetic and molecular changes implicated in

human cancer etiology and progression.

■ Accelerate the Mouse Cancer Genome

Anatomy Project to define the molecular

anatomy of mouse cancer models.

■ Provide funds to validate mouse models of

human cancer by systematic analysis and 

phenotyping.

■ Develop Mouse Models Application Funds to

test early detection, diagnostic, imaging, preventive, and therapeutic interventions in

mouse models.

■ Fund Phased Innovation Awards to develop

new tissue, cellular, and computational models of cancer.

7. Support the development of new technologies. 

■ Expand the Unconventional Innovations

Program to develop biosensors of human cancer and cancer development.

■ Fund an Unconventional Innovation Access

Program to apply technology discoveries to

clinical testing. 

■ Initiate a collaboration with the National

Aeronautics and Space Administration

(NASA) to develop minimally invasive

molecular biosensors.

PROGRESS IN PURSUIT OF 

OUR GOALS

The past several years have seen an explosion of

discovery in this area. NCI’s new and ongoing

initiatives include: 

■ The Institute’s flagship program for molecular

discovery is the Cancer Genome Anatomy

Project (CGAP). CGAP’s overall goal is to

determine the complete profile of expressed

(active) genes in normal, precancerous, and

cancer cells, with the aim of making it possible

to recognize all major steps of tumor development. Thus far, we have established the platform for building the complete molecular catalogue of cancer. Initially, we focused on cells

that directly give rise to tumors and placed

emphasis on five major types of cancer. Now

that the necessary infrastructure has been established, we are positioned to examine a much

wider variety of cancers and to extend our dis-
covery process to include cells that play key

supporting roles in cancer development, such as

the cells that form the tiny blood vessels that

feed tumors, cells that metastasize and the tissues that support those metastases, as well as

body fluids that might contain early indications

of cancer development. This new information

will greatly enrich our molecular catalogue of

cancer and make it even more useful to the

research community. 

CGAP is composed of five initiatives. The 

most established of these is the Human Tumor

Gene Index (TGI). Its primary goal is to identify the genes expressed during the development of human tumors. Data from the CGAP

have been used to discover approximately

30,000 new human genes. Other components of

CGAP include the Mouse Tumor

Gene Index, the Cancer Chromosome

Aberration Project, the Genetic

Annotation Initiative, and Molecular

Profiling. Each of these is described in

greater detail on the CGAP Web site.

■ NCI is creating a multi-institutional

Early Detection Research Network to

develop sensitive and specific tests for

the earlier detection of cancer. The

Network will link centers of expertise

in tumor biology, diagnostic technologies, and

clinical trials methodology in academia and

industry to develop high throughput assays suitable for clinical application. To expedite the

discovery and development of more sensitive

and specific markers for early disease, NCI also

will establish links between Network activities

and programs in academia and industry. 

■ In 1998, the NCI Director issued his Director’s

Challenge: Toward a Molecular Classification

of Tumors, a challenge to the research community to revolutionize the classification of human

tumors. Traditionally, tumor classification has

been based on morphology, or the tumor’s structure. But morphological classification alone

does not always accurately predict biological

behavior, treatment response, or prognosis. We

anticipate that the research community will rise

to this challenge and discover new ways to

combine technological advances in molecular

detection with rapidly advancing knowledge of

tumor biology to provide a more clinically predictive and useful tumor classification system.

■ Success in developing molecular diagnostics

depends on the availability of specimen banks

for tissue analysis. NCI has several programs

designed to collect and disseminate tissue, such

as the Cooperative Breast Cancer Tissue

Resource. NCI also will develop a national

prostate cancer tissue resource. In addition,

NCI sponsors the Tissue Expediter, a scientist

whose role is to identify sources of human tissue

specimens and to help researchers locate the

tissue and related data they need. 

■ Models that truly reflect the behavior of human

cancer and its response to preventive and therapeutic maneuvers would profoundly

improve our ability to understand the

process of malignant transformation, and

could enhance our ability to evaluate a

range of biomarkers prior to their clinical

application. To meet the need for animal

models in a variety of settings, NCI is

soliciting applications for establishing a

consortium that will develop and validate mouse models for human cancer.

■ New technology development is key to

success in this area. Many new technologies will be supported through NCI’s

Phased Innovation Award, developed last year

to support technology research from the evolution of innovative concepts, through feasibility

testing, and ultimately to subsequent full-scale

development. In its first year, this mechanism

already has reduced significantly the time lag

between the review process and application

funding, and is expected to continue accelerating the pace of technology development for

profiling molecular characteristics of preneoplastic cells. A similar award, the Phased

Technology Application Award, has been 

created to support the pilot application of

instrumentation, techniques, and analytic tools 

(e.g., computer software) relevant to research

on the molecular biology of cancer.

54 The Nation’s Investment in Cancer Research

For more CGAP

information, 

visit

http://www.

ncbi.nlm.nih.

gov/CGAP
Extraordinary Opportunities 55

Opportunities

Resources: Defining the Signatures of Cancer Cells

Characterize the molecular profiles of precancerous and cancerous cells. $16.0 M 

■ Complete the Tumor Gene Index.

■ Enhance Director’s Challenge to establish molecular profiles of human cancer and develop molecular classification schemes for all human cancers.

■ Develop data bases and analytic tools.

Establish and make available tissue resources. $7.0 M

■ Establish and promote a national system.

■ Develop public education materials about tissue donation for research.

Develop and deploy molecular pathology informatics system. $3.0 M

■ Establish standardization and common data elements. 

■ Provide automatic encryption features.

■ Establish linkages to population-based data resources.

Create new classification system for cancer; use it to model improved 

approaches to detection, diagnosis, and prognosis. $20.5 M

■ Initiate a Director’s Challenge to identify molecular signatures of preneoplastic lesions. 

■ Expand the Early Detection Research Network.

■ Develop repositories, assays, and new technologies.

■ Develop standards for correlating molecular and pathologic criteria used to stage cancer.

Validate potential molecular signatures. $16.0 M

■ Create Diagnostics Validation Network.

■ Provide supplemental funding to groups to evaluate biomarkers.

Develop preclinical models. $15.0 M

■ Accelerate the Mouse Cancer Genome Anatomy Project.

■ Develop Mouse Models Application Funds to test early detection, diagnosis, prevention 

and treatment interventions.

■ Develop new tissue, cellular, and computational models of cancer.

Support technology development. $11.5 M

■ Expand the Unconventional Innovations Program to develop biosensors.

■ Fund an Unconventional Innovation Access Program to apply discoveries to clinical testing.

■ Collaborate with NASA to develop minimally invasive molecular biosensors.

Management and support. $4.0 M

TOTAL $93.0 M
CANCER OR PRECANCEROUS LESION

1 Define Molecular Signatures: Identify 

cell pathways important to cancer

2Identify Molecular Targets: Target pathways 

critical to cancer development and progression

3 Develop High-Throughput Screens for High-Priority 

Targets: Develop assays to detect effects of drugs on targets

4Screen Thousands of Chemicals and Biologicals: Use highthroughput assays to identify agents that hit priority targets

5Identify the Best Drug Candidates

for Preclinical Development

6Laboratory Testing and Preparing for Human Trials: Turn a

candidate into a drug suitable for clinical testing

7Phase I Clinical Trial: Study 

safety, toxicity, pharmacology

8Phase II Clinical Trial: 

Study anti-cancer effect

9Phase III Clinical Trial: Study efficacy 

compared to standard approaches

10 Widespread 

Clinical Use

56 The Nation’s Investment in Cancer Research

The Path to a New Cancer Drug

The pathway to the development of a new treatment or

preventive drug begins at the cell. All cells have unique

signatures composed of all the genes that are active, proteins that are secreted, processes that are followed, and

pathways that are present. A cancer cell’s signature differs

from that of a normal cell; different genes are active or

inactive, for example, or different pathways may be present. Certain components of a cancer cell’s signature –

genes, pathways, or patterns of behavior – may be especially vulnerable to the action of treatment or preventive

agents. These components are the molecular targets at

which treatments or preventives can be aimed.

In developing a new anti-cancer drug, scientists

must first identify and understand the cell’s true 

signature before choosing the molecular target (2).

Once a target is identified, we can 

screen thousands of agents (3,4) in 

the laboratory to determine which agents

are effective against the target (5). 

Extensive laboratory testing of the most promising agents follows, beginning in the test tube,

then moving to living systems such as mice (6).

If an agent continues to show promise, it makes 

the next steps to testing in humans (7-9) 

(see page 27 for an explanation of clinical trials).

Finally, if the agent is proven safe and

effective, it becomes a regular part of

our arsenal against cancer (10).
Extraordinary Opportunities 57

Opportunities

Molecular Targets of Prevention and Treatment 4 OPPORTUNITY

THE OPPORTUNITY

Our systematic search for drugs to combat cancer began about 60 years ago. During most of

this search, our understanding of cancer has been

limited by technologies available at the time – the

microscope enabled us to see the structure of the

cancer cell, but our ability to discern the once

normal features and internal pathways that had

become corrupted was incomplete. As a result, our

techniques for identifying drugs to prevent or treat

cancer were rate-limiting, involving tests that

measured inhibition of cancer’s development or its

growth in animals or test tubes. Despite these limitations, scientists have identified drugs that, alone

or with surgery, can cure some cancers in people

and can significantly ease symptoms in others. 

Yet anyone who has ever undergone treatment

for cancer – or watched a loved one undergo treatment – knows that our ability to treat the disease

leaves much to be desired. Most of the common

tumors of adults – the ones that cause most of the

suffering and death from cancer – do not respond

well to the treatments available today. And even

when these treatments succeed in shrinking

tumors or eliminating them from the body, they

can cause a variety of short- or long-term side

effects that can have a devastating impact on a

patient’s quality of life. 

Many of the serious side effects of cancer treatments stem directly from their non-selective

nature. Until recently, we were unable to detect

the differences between the molecular features of

normal and cancerous cells, and thus, a compound

that inhibited the growth of a tumor cell also

inhibited the growth of a healthy cell. This is

what causes many of chemotherapy’s most severe

toxic effects. However, drugs that target the

molecular differences between tumor and normal

cells – the altered genes or proteins or the corrupted pathways – would be less toxic and more effective than the drugs we currently have. 

The situation for prevention is similar. The

recent findings that the anti-estrogen tamoxifen

can reduce the risk of invasive breast cancer suggests that cancer prevention is a realistic possibility. If we know the precise molecular steps that

characterize premalignant change, we can attempt

to find agents that reverse these changes or prevent next steps critical to the full development of

cancer from occurring. This new generation of

chemopreventives will be optimized and made

more efficient by clinically testing the effect of a

preventive on its intended target. 

Until recently, scientists working to discover

effective prevention and treatment agents have

faced a formidable barrier: not knowing precisely

what cancer is. No longer is this the case. With

the evolution of molecular biology and the emergence of new technologies, we are gathering

remarkable knowledge about the nature of a cancer cell and the molecular changes that occur during a tumor’s development. The extraordinary

opportunity before us – to discover and exploit

molecular targets for cancer prevention and treatment – arises from the convergence of scientific

advances in several areas.

Cancer Biology

We continue to make astounding strides in our

understanding of how molecules and pathways in

premalignant or fully malignant cells differ from

their normal counterparts. This new knowledge is

enabling us to understand and classify human

tumors in terms of molecular changes and also has

given us a new strategy for cancer drug discovery.

Today, every difference between cancerous and

normal cells is not only a biological fact or a point

of interest to the biochemist, it is a potential target of opportunity for drug discovery. 

Synthetic Chemistry

Traditionally, the chemicals used in anti-cancer

drugs have come from nature – from tropical rain
forests or organisms in the sea or the soil. Using

recently developed techniques, chemists now are

able to create in the laboratory enormously diverse

collections of compounds. Now, both naturally

and synthetically derived chemicals can be

screened for possible anti-cancer effects. The 

ability to test the effectiveness of large numbers 

of structurally diverse compounds – using highly

informative cancer-relevant techniques that

exploit our knowledge of cancer biology – is now 

a reality.

Biosynthetic Chemistry

Synthetic chemists have long been able to manipulate small molecules to produce useful medicines.

The recent biotechnology revolution has cleared

the way for biochemists to mix and match genes

to design synthetic proteins. Changing proteins in

cells is an important breakthrough, since proteins

form the “messages” that make up communication

pathways that determine a cell’s healthy or aberrant behavior. Historically, scientists have been

unable to alter these messages since they only had

access to proteins produced naturally within cells.

Now scientists can change the messages sent by

protein molecules, creating a whole new class of

drugs to be tested for anti-cancer activity.

High Throughput Screening

Over the past decade, advances in biotechnology

have made it possible to devise highly sensitive,

highly efficient tests for virtually any biological

process. These tests, or “smart” assays, can be used

many different ways. For example, they can be

used to screen cell lines and tissues for the presence of particular genes, proteins, or entire pathways – an essential step in identifying the chain of

events involved in every stage of cancer development. These assays also can be used to screen

potential drugs for anti-cancer effects; thousands

of compounds can be screened in this manner

each week. Moreover, these assays can be performed on a micro scale with tiny quantities of

material, using computer-driven robots to maximize efficiency. 

Medical Imaging

Until now, imaging has been used in cancer

research and care to gain information about the

occurrence, size, and location of tumors.

Refinements in imaging technology are allowing us

to watch molecular processes within the cell unfold,

as they occur, with unprecedented vividness and

accuracy. Imaging techniques are being developed

to tell us not only the location of a tumor but the

kind of molecules it contains and how its biochemical pathways work. Further advances will have a

profound impact on the testing of potential cancer

interventions. For example, new imaging technologies have the potential to track where drugs go in

the body, or visualize a drug’s immediate effects on

abnormal collections of cells and on normal tissues.

These uses of such functional imaging approaches

are likely to be as common in the future as the use

of the CT scan is now. 

The convergence of these advances presents us

with the opportunity for a real revolution: to place

the discovery and development of drugs for cancer

prevention and treatment on a firm scientific footing. There is good reason to think that doing so

may, within the next decade, lead to a whole new

generation of cancer treatments and preventives.

Yet, to ensure our success, we need to create conceptual and functional links among drug discovery,

development, and clinical testing in ways that are

completely unprecedented. 

To understand why, consider the main questions that researchers need to pursue about a new

drug’s effect on malignant or precancerous cells.

Does the drug kill the cancer, or at least effectively

block its growth and spread? What part of the

cell’s complex machinery does it disrupt and how

is this disruption related to its anti-cancer effect?

Until now, with our incomplete knowledge of cancer, we had neither the knowledge nor the tools to

address this second question, and thus, our clinical

testing focused only on the first.

It is crucial that we gather the knowledge and

develop the tools to answer both of these questions. When we can, we will finally be able to

address some of the most important questions in

cancer therapeutics. If a drug is working well, why

is it working, and if not, why not? Are we giving a

person the right amount, or too much, or too little? Do we have to give people the maximum

amount of a drug that they can tolerate, or can we

judge the right amount by whether the drug is getting to the tumor and affecting its target? Will the

drug harm the patient, now or in the future? Only

when we can answer these questions will we be

58 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 59

Opportunities

able to predict who is likely to respond to a 

particular treatment and who will not. Moreover,

information from the clinic and from the laboratory will reinforce each other, providing the basis for

the design of even better drugs in the future. 

Timely investment in this area is critical. If the

NCI does not invest now, engaging academicallybased cancer biologists will depend on the alignment of their discoveries with the product development goals of individual companies. This

process will be incomplete and will not necessarily

emphasize the compounds, hypotheses, or

approaches that are likely to yield the most farreaching advances. Because most companies’

efforts are highly focused, many important scientific opportunities will not be explored in a timely

manner. Most importantly, development of the

practical tools needed to enable assessment of a

drug’s effects on its molecular target in vivo will

not happen quickly or systematically, and information and reagents will not be made publicly available as soon as they might have been.

THE GOALS

■ Transform the process by which cancer therapeutics and preventives are discovered, developed, and tested in the clinic. 

■ Base discovery and development on interference with specific molecular targets in premalignant and malignant cells and in the tissues

surrounding the malignancy that sustain its

growth and spread.

■ Expand the involvement of the entire cancer

research community in the discovery and development process.

THE PLAN

Objectives

1. Identify and characterize molecular targets 

for drug discovery. 

■ Fund Molecular Target Discovery Grants to

provide researchers working on cancer mechanisms with the resources to develop the evidence that a new cancer-relevant molecule or

pathway is, in fact, a promising target for drug

discovery. Such evidence will establish the

credentials of a molecule or pathway as a suitable target for prevention or treatment discovery efforts.

■ Supplement existing grants to support the

synthesis of target molecules in sufficient

quantities necessary to characterize them 

biologically and determine their physical

structure.

■ Supplement existing grants for structural

studies involving collaborations between 

cancer biologists and structural biologists to

determine the physical structure of target

molecules through x-ray crystallography or

nuclear magnetic resonance. 

■ Convene a panel of experts to assist NCI in

prioritizing the targets emanating from this

program, to pinpoint those worthy of further

research and development.

2. Develop assays (tests) for molecular targets.

■ Contract with organizations expert in stateof-the-art drug screening technology to develop sensitive, high throughput assays for priority molecular targets to assess the effects of

compounds on a target. The result of this

effort will be a practical screen for every high

priority target, through which thousands of

compounds can be tested daily.

3. Establish chemical and biochemical 

diversity libraries.

■ Assemble and curate a “Library of Libraries” –

a rich collection of small molecule chemical

libraries derived from combinatorial synthesis

programs. The library, assembled in collaboration with chemists from academia and industry, will complement NCI’s existing repositories of natural product extracts and synthetic

chemicals. These libraries will be formatted

to be suitable for screening and will be widely

available to researchers.

4. Foster interactions between assay developers

and diversity libraries. 

■ Make diversity libraries widely available to

researchers with assays. Create a sophisticated

informatics system annotating the chemical

repositories to ensure researchers’ access to

libraries most appropriate for their scientific

orientation. NCI staff and outside experts

will work together to match biologists with

innovative assays to chemists having libraries

of potential relevance to those assays. 
■ Double the number of Chemistry-Biology

Centers in which chemists and biologists 

create highly integrated programs that combine chemical diversity generation with the

use of these compounds in “smart” high

throughput screens.

5. Screen compound libraries. 

■ Fund contracts for drug screening to identify

chemicals or biologics that hit our priority

targets. Use the assays developed with our

support to screen compound libraries from

our collections. The most promising compounds identified from this process will

undergo chemical optimization, and the best

optimized compounds will be developed into

drugs suitable for clinical testing. 

6. Create the tools and methods to make possible

target-based clinical testing.

■ Establish Centers of Excellence for Drug

Development organized around a mechanism

of particular relevance to cancer prevention

or therapy, such as angiogenesis, cell-cycle

control, immunotherapy, DNA-damage

repair, cell signaling, differentiation, 

metastasis, or apoptosis. These multidisciplinary research groups of chemists, biologists,

pharmacologists, imagers, clinicians, and

informatics experts will create the tools 

necessary to clinically assess and validate the

effects of drugs on molecular targets. All

reagents developed in these centers will be

made available to the research community. 

■ Provide supplements to Centers of Excellence

for Drug Development. Supplements will

enable a Center to work with other investigators and NCI to develop specific compounds.

Companies will be able to provide resources

to the Centers for similar collaborations.

■ Increase support to the National Cooperative

Drug Discovery Group program. This NCIfunded program supports consortia of academic institutions and pharmaceutical companies

discovering and developing targeted drugs.

7. Expedite the steps that turn a chemical 

or a biologic into a drug suitable for initial

clinical testing. 

■ Fund contracts for drug-lead optimization and

drug development. Contracts with chemists

in academia and industry will support optimizing lead structures produced by targetbased discovery activities that result in candidate compounds for clinical testing. NCI’s

contracts program for pharmacology, synthesis, formulation, and toxicology will support

the advancement of these drug candidates to

the clinic. Fast-response contracts will assist

in developing assays for particular agents in

NCI’s development pipeline.

■ Support optimization of target-directed biomolecules. NCI will increase support for optimization of the interaction of biomolecules

(for example, monoclonal antibodies) with

their targets by exploring the effects of

sequence diversity on important properties

like target affinities and selectivity.

■ Competitively fund Rapid Access to

Intervention Development (RAID and

RAPID) contracts for academic drug discovery laboratory needs. The contracts will support novel discoveries through the development steps necessary to take a new discovery

into the clinic for proof-of-principle testing as

a potential therapeutic or preventive.

8. Expand Resources and infrastructure.

■ Create standards and expedite access to biological resources. The availability of standardized reagents (cell lines, growth factors) or

assay conditions is critical to further progress.

In collaboration with the investigator community and with industry, NCI will create

standards for assays and reagents. If access is a

significant research barrier, NCI will create a

distribution system to expedite access to crucial reagents at reasonable cost.

■ Fund synthesis of chemicals and biologicals

and provide them to the research community,

on a competitive basis, to advance the drug

discovery effort and move promising compounds to clinical trials.

■ Develop data bases of drug screening results

and create a publicly accessible Web site that

advertises the availability of chemical and

biological resources and expedites interactions between research groups.

60 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 61

Opportunities

Identify and characterize molecular targets for drug discovery. $7.5 M

■ Fund Molecular Target Discovery Grants (R01, R21/R33, SBIR/STTR).

■ Fund up to 5 grant supplements to support the synthesis of target molecules.

■ Fund up to 5 grant supplements to determine the physical structure of target molecules.

■ Convene a panel of experts to assist in prioritizing targets.

Develop assays for priority molecular targets. $0.5 M

■ Develop sensitive, high throughput assays.

Establish chemical and biochemical diversity libraries. $2.0 M

■ Assemble and curate a collection of small molecule chemical libraries derived from combinatorial

synthesis programs.

Foster interactions between assay developers and diversity libraries. $6.5 M

■ Make diversity libraries widely available to researchers with assays. 

■ Double the number of Chemistry-Biology Centers (U19).

Screen compound libraries. $0.6 M

■ Fund drug screening contracts to identify chemicals or biologics that hit priority targets.

Create tools and methods for target-based clinical testing. $22.5 M

■ Establish 10 Centers of Excellence for Drug Development (P50).

■ Supplement P50 grants for Centers of Excellence for Drug Development to support collaborations.

■ Increase support to the National Cooperative Drug Discovery Group program.

Expedite steps that turn a chemical or biologic into a drug suitable for 

initial clinical testing. $20.5 M

■ Fund contracts for lead optimization and drug development.

■ Support optimization of the interaction of biomolecules with their targets.

■ Fund RAID and RAPID contracts for drug development needs of academic discovery laboratories.

Expand resources and infrastructure. $4.3 M

■ Create standards and distribution system for biological resources. 

■ Synthesize and provide chemicals and biologicals to research community.

■ Develop data bases of drug screening results; create publicly accessible chemical and 

biological resources Web site.

Management and support. $2.0 M

TOTAL $66.4 M

Resources: Molecular Targets of Prevention and Treatment
THE OPPORTUNITY

The numbers are truly alarming. Every day,

across this country, more than 3,000 youths

will begin to smoke, placing themselves at

increased risk for a host of cancers – lung, mouth,

pharynx, larynx, esophagus, pancreas, cervix, kidney, and bladder – as well as heart disease and a

range of other conditions. Of those who continue

to smoke, approximately one half will die prematurely, losing an average of 20 to 25 years of their

life expectancy. And an estimated 450,000 people

in the U.S. will die this year alone from tobaccorelated diseases – the most preventable and costly

cause of death in our Nation. The global picture is

even more sobering: More than one billion people

smoke worldwide and an estimated three million

die annually from tobacco-related illness.

By 2025, the number of deaths is expected to reach ten million per year.

These statistics illustrate dramatically

that tobacco – through the use of cigarettes, cigars, pipes, and smokeless products – poses an extremely serious threat to

people’s health worldwide. They also

underscore the urgency of addressing this

threat. Evidence demonstrates strongly

that people who stop smoking – regardless

of age – live longer than those who continue to

smoke, although their risk for lung cancer remains

somewhat higher than if they never had smoked.

To respond to this major threat to life and health,

NCI has established decreasing tobacco use as an

area of extraordinary opportunity. 

Seizing this opportunity, however, presents a

significant challenge to NCI and to the research

and public health communities. In a field where

every need seems pressing, we must identify where

research is most needed and how best to prioritize

and achieve scientific objectives with the greatest

benefit. As a first step, NCI established the

Tobacco Research Implementation Group

(TRIG), bringing together two dozen leading scientists and experts to identify tobacco-related

research priorities for the next five to seven years.

The TRIG identified and prioritized a set of nine

overarching research opportunities. Pursuing these

priorities promises to alter dramatically the way

tobacco research is conducted on a national scale

and to speed the pace of discovery to help reverse

today’s epidemic of tobacco use and tobacco-related cancers. 

Developing Optimal Prevention and

Cessation Strategies

Studies indicate that the majority of smokers want

to stop smoking completely but struggle to quit.

And most adolescents who smoke regret ever

starting. Thus, developing strategies that prevent

people from ever starting to smoke and

help those who currently smoke to stop 

is a critical need.

In the last three decades, we have witnessed many achievements in this area of

research: the development and implementation of physician training and office protocols for smoking cessation programs; the

confirmation of the effectiveness of primary care medical and pharmacologic

interventions; the development of effective self-help interventions; and the development

of new tailored, proactive interventions designed

to meet the needs of individual smokers. In addition, mass media interventions capable of reaching

large numbers of people with prevention and cessation messages have been developed and strategies aimed at reaching minority, ethnic, and highrisk populations have been tested. Recent large

programs, like the Community Intervention Trial

for Smoking Cessation (COMMIT) and the

American Stop Smoking Intervention Study

(ASSIST), have shown both the potential and the

limitations of community and state tobacco control interventions for changing attitudes about

5 Research on Tobacco and Tobacco-Related Cancers 

OPPORTUNITY

62 The Nation’s Investment in Cancer Research

For more 

information on

TRIG, visit

http://dccps.

nci.nih.gov/

tcrb/TRIP/
tobacco use, changing tobacco use behaviors, and

reducing the tobacco-related cancer burden. Yet

we still do not fully understand the most critical

elements of tobacco prevention and treatment

strategies, their timing, how best to target highrisk subgroups and settings, and how to tailor messages and materials appropriately for different populations. 

Identifying and Targeting Populations at

High Risk for Tobacco-Related Cancers

and Nicotine Addiction

We have made enormous progress in understanding the molecular and genetic factors that underlie

the transformation of a normal cell to a cancer

cell following exposure to tobacco carcinogens.

For example, scientists have identified many cancer-causing agents contained in tobacco smoke

and shown that different tobacco products and

methods of nicotine delivery influence the type

and quantity of exposure to these agents. 

Researchers also have determined that these

multiple agents seemingly induce similar changes

in a cell, regardless of the cell’s location in the

body. The challenge now is to learn more about

how and why elements in tobacco smoke target

particular genes and how tobacco-induced cellular

damage initiates and promotes cancer’s development. Such knowledge, gained through studies

using preclinical models, will help us identify precancerous lesions and markers that may predict

tobacco-induced cancer. Identifying markers that

detect DNA damage and other antecedents of cancer will enable us to test different prevention and

treatment strategies and develop new early detection methods. It also will enable us to determine

the amount of carcinogens in different tobacco

delivery systems, the effects of burning temperatures on tobacco additives, and how tobacco smoke

components interact with each other. 

This research also could provide important

insights into why some people may be particularly

vulnerable to harm from tobacco. For example,

women develop more lung cancers than men per

cigarette smoked. Certain ethnic groups appear to

be at increased risk for lung cancer as well. While

the reasons for these differences are not clear,

smokers with certain gene variants are more likely

to be lung cancer victims. Therefore, we need to

develop preclinical models that will enable us to

identify the harmful variants that lead to increased

susceptibility to tobacco-related cancers to help

determine why some individuals exposed to tobacco are particularly susceptible to cancer, while

others are spared. Using this information and

knowledge of how inherited susceptibilities and

tobacco exposure contribute to cancer in combination, we can develop specific prevention and

detection strategies and target them to vulnerable

individuals. 

Further, there is increasing evidence that genes

interact with environmental factors to influence

whether an individual will start smoking, how

early he or she will start, and how difficult it will

be for him or her to quit. Just as we now know

more about the biological bases of tobacco-related

cancers, we also have learned a great deal about

the psychosocial, biobehavioral, and biological

determinants of tobacco use and addiction. We

know, for example, that adolescent tobacco use is

tied to peer and family influences and low selfesteem. We also know that continued smoking by

adults is associated with nicotine addiction,

depression, and stress. More recently, major

research breakthroughs have provided important

Extraordinary Opportunities 63

Opportunities

About Tobacco

■ Tobacco is responsible for more than 30 percent 

of all cancers and nearly one in five deaths in the 

U.S. every year.

■ In the last decade, more than four million people in

this country lost their lives to tobacco-related diseases,

including, according to Environmental Protection

Agency estimates, more than 30,000 nonsmokers 

who died of lung cancer caused by breathing smoke

from others’ cigarettes.

■ The number of tobacco-related deaths in the U.S. 

continues to rise, particularly among women.

■ The financial costs of tobacco also are rising. Over 

the course of their lives, current and former smokers

generate an estimated $501 billion in excess health

care costs. Tobacco costs Medicare a staggering 

$10 billion each year and Medicaid more than 

$12.9 billion annually.

■ Smoking among U.S. adolescents has increased by 

73 percent in the last 10 years, and the declines in

adult smoking appear to have leveled off. 

■ Rates of smoking are disproportionately high among

certain population groups, such as African Americans.
64 The Nation’s Investment in Cancer Research

My father was just diagnosed with

lung cancer. He quit smoking twenty years ago — we never dreamed

he would still be at risk. 

Cigarette smoking is by far the single

greatest risk factor for lung cancer,

which will cause nearly 160,000

deaths this year. Current smokers are

at highest risk, but lung cancer does

occur in former smokers even years

after they have quit. Research is

urgently needed to determine how to

decrease the risk of tobacco-related

cancers in former smokers, who now

number nearly 50 million. Research

also is needed to find these cancers

when they are small and curable. Lung

cancers can occur in people who have

never used tobacco. Other factors

shown to increase lung cancer risk

include recurrent lung inflammation,

air pollution, exposure to radon gas

(especially in combination with tobacco smoke), and exposure to asbestos

and other industrial carcinogens.

We found out about a clinical trial of

a new treatment for people with the

kind of lung cancer my father has –

the early results look promising.

Treatment for both major types of

lung cancer – small cell and nonsmall cell – remains extremely difficult, but we are achieving modest

incremental improvements. Advances

in combination chemotherapy and

radiation regimens have played the

most significant role in treating small

cell lung cancers, while refined surgical techniques have been most important in improving the outlook for

some patients with early non-small

cell lung cancer. Other advances may

be on the horizon. Early study results

suggest that

photodynamic

therapy – the

use of lasers and

light-activated

drugs to kill

tumors – may

hold promise for

certain groups of

patients with

early lung cancers and for

some patients

who cannot

withstand surgery. In another

early clinical

trial, administration of a genetically altered

virus successfully replaced faulty 

p53 tumor suppressor genes in

patients with advanced lung cancer,

leading to disease stabilization or

tumor shrinkage for some patients,

and in one case, complete remission

of disease. Though more research is

needed to demonstrate their benefit,

approaches such as these may eventually offer lung cancer patients new

treatment options.

I smoke. I know it sends the wrong

message to my daughter. 

Each day, 3,000 American youth

become smokers. If they continue to

smoke, as many as half will eventually

die a premature, tobacco-related

death – many of these deaths will

result from lung and other smokingrelated cancers. Cigarette smoking is

again increasing among teenagers,

and recent evidence indicates that

smoking rates also are rising markedly

among college students. New studies

show that people who begin smoking

as adolescents are more susceptible

to long-term DNA damage associated

with lung cancer. Smoking among

women continues to escalate, as does

their lung cancer incidence and mortality, which exceeds that of breast

cancer. Moreover, cigar smoking,

which increases risks of lung and oral 

cancers, is increasing among both

women and men. Recently, a gene has

been discovered that appears to

affect how easily a person becomes

addicted to nicotine.

People’s Story

Lung Cancer
Extraordinary Opportunities 65

Opportunities

Especially now, since my father’s

diagnosis, I want to try to quit

smoking. I’ve failed so many times

before, but I think this time will be

different. 

Nearly a quarter of the U.S. adult

population smokes, but most smokers

want to quit. Furthermore, nearly one

third of all cigarette smokers attempt

to quit each year, but only a small

percentage actually succeed. New

smoking cessation aids have become

available in recent years to help

smokers – nicotine gum, the nicotine

skin patch, the antidepressant drug

bupropion, and smokeless nicotine

inhalers. A recent study found that

after one year, almost 36 percent of

those using the patch and bupropion

together remained abstinent, compared to those using bupropion alone

(30 percent) or the patch alone (just

over 16 percent). Evidence also indicates that quitters using a cessation

aid who also get counseling from

their health care provider have better

success than those who do not.

Following the recommendations of its

Tobacco Research Implementation

Group (TRIG), NCI, in collaboration

with the National Institute on Drug

Abuse, will soon launch a network of

Transdisciplinary Tobacco Research

Centers to study tobacco use initiation and prevention, tobacco addiction and its treatment, and the treatment of tobacco-related cancers. The

TRIG also has recommended targeted

research initiatives to identify cultural, psychological, and genetic factors

that influence smoking behavior in

children and adults. Other initiatives

will focus on improving the dissemination of proven prevention and

treatment interventions at the state

and community levels, and on tailoring tobacco control programs for 

populations at high risk.

I’ve learned that even if I never

smoke again, my lung cancer risk

may always be higher than someone

who never smoked. My doctor told me

some signs of trouble to watch for. 

Though most lung cancers cause no

symptoms until they are advanced,

smokers and former smokers should be

especially alert for symptoms that may

signal early lung cancer. These include

a persistent cough, hoarseness, chest

pain, loss of appetite and weight loss,

bloody or rust-colored sputum, shortness of breath, fever without apparent

reason, recurring bronchitis or pneumonia, and wheezing. Any of these

symptoms can be caused by other diseases, but seeing a doctor promptly is

the only way to find out if they are

being caused by a lung cancer.

Watching for such signs is especially

important since no reliable procedure

for routine lung cancer screening is

yet available. Encouraging results

from an early trial of spiral computed

tomography (spiral CT) for lung cancer detection suggest that further

developing this technology may lead

to an affordable, accurate lung cancer

screening test in the coming years. 

Research also is being conducted to

learn more about former smokers’

long-term risk for lung and other cancers. In addition, for those lung cancers not attributable to tobacco use,

NCI is continuing research to learn

more about how genes, the environment, and other factors may contribute to lung cancer development

and progression.

This vignette is a composite of 

experiences.

Annual Percent Change in Mortality 

Lung & Bronchus Cancers 1990-1996

All Races

Significant Yearly Increase

No Changes

Significant Yearly Decrease

MALES FEMALES
insights into the biological bases of tobacco use

and nicotine addiction, including the role of

genetic factors and ethnicity in nicotine metabolism. For example, researchers have identified

genes that modify nicotine metabolism and regulate brain chemicals that affect the pleasurable

feelings triggered by nicotine. These discoveries

provide unique opportunities for studying the links

between biology and behavior and will help identify preexisting vulnerabilities to tobacco use. By

determining how these vulnerabilities interact

with sociocultural and psychological influences on

tobacco use, and by improving our ability to assess

risks quantitatively, we can develop more effective

prevention and cessation interventions and tailor

these interventions to the people most likely to

benefit from them. We also can identify effective

new drugs and combinations of already proven

drugs for treating nicotine addiction. The combination of pharmacologic and behavioral tailoring

may be particularly important in accelerating

major improvements in smoking cessation rates. 

Capitalizing on Social, Legal, and 

Public Policy Developments

A number of social, legal, and public policy developments are converging with scientific advances

to create a unique opportunity to tackle tobacco

use. Public attitudes reflect decreasing acceptance

of tobacco use as a social norm. For example, concerns have been raised about the targeted marketing of menthol cigarettes in the African American

community. Government agencies, academic institutions, and professional and voluntary organizations are making major commitments to reduce

tobacco use and exposure to tobacco carcinogens.

Through lawsuits, states are recovering billions of

dollars lost to the treatment of diseases caused by

smoking. However, while state political leaders

have been urged to use these funds to expand

tobacco control programs, they almost certainly

will use most of the funds to address other priorities. This dilemma underscores the need for NCI

to expand its investment in tobacco control

research to ensure that the best scientific evidence

informs state and community programs. How can

we help policy makers develop effective programs

when we do not know the full impact on tobacco

use of clean indoor air policies, marketing restrictions, and youth access restrictions, all of which

are pillars of tobacco control but face stiff and

sometimes passionate resistance? 

In summary, we have an unprecedented opportunity to reduce the enormous burden of tobacco

use on our Nation’s public health. The investment

proposed here will enable us to gather knowledge

that will inform policy makers and public health

practitioners about the best strategies for prevention and treatment; this is of special concern

because states must decide how best to use tobacco

company settlement funds for tobacco control

efforts. Our collaborations with Federal and state

officials will help ensure that these funds are spent

in ways that will maximize tobacco control benefits and save lives.

More effective smoking cessation programs

alone could save many of the nearly 160,000 lives

lost to lung cancer each year. An expanded tobacco control research program covering biological

and biobehavioral research; clinical, epidemiologic, surveillance, and policy research; and support

for research infrastructure, will be essential to

achieving our goals. 

THE GOALS

■ Define the biological, behavioral, and societal

bases of tobacco use and addiction.

■ Reduce tobacco use rates among youth and

adults, and especially among high-risk groups

including low income, minority, and medically

underserved smokers.

■ Define the relationship between exposure to

tobacco products and carcinogenesis. 

■ Prevent cancer in former smokers.

THE PLAN

Objectives

1. Develop more effective interventions to 

prevent tobacco use.

■ Initiate trans-NIH efforts to determine the

interdependent causes of tobacco use, especially among youth. These efforts should

include epidemiological studies, such as longitudinal cohort designs, to track familial,

environmental, and biological risk factors

within the same individuals over time,

66 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 67

Opportunities

enabling us to better understand the determinants and health consequences of tobacco use

in children and adults. 

■ Fund a consortium of prevention scientists to

develop targeted tobacco use prevention

strategies for high-risk populations.

■ Establish a tobacco policy research consortium to determine the impact of pricing policies, clean air policies, marketing and access

restrictions, and tobacco product and nicotine replacement regulation on tobacco use.

2. Develop more effective strategies for tobacco

cessation, including those tailored for highrisk individuals.

■ Develop more powerful pharmacotherapies by

discovering new drugs, combining proven

drugs to determine additive effects, and

studying long-term use to improve cessation

maintenance. 

■ Develop new behavioral techniques and technologies that will amplify the effects of other

treatments; tailor therapies to smoker characteristics such as age, race and ethnicity, culture, income, education level, psychiatric cofactors, other diseases, and even genetic

makeup.

■ Conduct controlled intervention trials to

identify optimal ways to disseminate and

implement proven tobacco-use prevention

and treatment strategies. 

3. Expand initiatives exploring genetic/environmental interactions that influence smoking

behavior and increased risk for cancer.

■ Support research to identify genes related to

addiction.

■ Fund studies to understand how environmental and other factors interact with genes to

influence the likelihood and age of smoking

initiation, intractability of addiction, and risk

of tobacco-related disease, such as lung cancer.

■ Encourage collaborations with international

investigators to enable us to pursue unique

research opportunities involving resources

not available in the U.S. 

4. Develop approaches to prevent cancer in 

former smokers.

■ Expand NCI’s Early Detection Research

Network to identify and validate markers of

tobacco exposure and tobacco-induced cellular events leading to carcinogenesis.

■ Support preclinical model development and

small clinical trials to test preventive agents

or cancer therapies for people with a history

of tobacco exposure and the highest risk of

developing cancer.

■ Fund innovative studies to determine the

mechanisms by which tobacco use contributes to the development of non-aerodigestive cancers such as pancreas, cervix, and

bladder cancers. 

5. Expand the national research infrastructure to

support tobacco use research across disciplines, provide training to new investigators,

and monitor trends in tobacco use and tobacco-related cancers.

■ Expand support for transdisciplinary tobacco

use research and training. 

– Use the Transdisciplinary Tobacco Use

Research Centers (TTURCs) to bring

together and foster collaboration among

transdisciplinary teams of scientists.

Establish new TTURCs to expand the

scope of research conducted at existing

TTURCs.

– Support transdisciplinary research through

other mechanisms and increase support for

training in tobacco research, especially

among minority investigators. 

– Establish a clinical research program at

NCI where scientists from NIH and the

extramural community can collaborate and

rapidly implement cutting-edge research on

nicotine addiction and tobacco use.

■ Expand surveillance systems to monitor

tobacco use behaviors, the implementation

and durability of tobacco-related interventions, and other factors that influence 

tobacco use.
68 The Nation’s Investment in Cancer Research

Resources: Research on Tobacco and 

Tobacco-Related Cancers

Expand research on tobacco use prevention. $11.0 M

■ Initiate trans-NIH effort to determine interdependent causes of tobacco use.

■ Fund a consortium to develop targeted prevention strategies for high-risk populations.

■ Establish a tobacco policy research consortium.

Develop improved tobacco-use treatment strategies. $12.0 M ■ Develop and evaluate new drug and drug combination treatments for tobacco addiction.

■ Develop tailored behavioral techniques, technologies, and treatments.

■ Conduct controlled intervention trials.

Conduct genetic epidemiology research. $6.0 M

■ Supplement research grants to accelerate the discovery of nicotine addiction-related genes. 

■ Establish cohorts to study the etiology of tobacco use.

■ Initiate international collaborative studies to identify genes-environment interactions influencing

tobacco use initiation, cessation, and cancer development.

Prevent cancer in former smokers. $4.0 M

■ Expand Early Detection Research Network to identify and validate markers of tobacco 

exposure and carcinogenesis.

■ Support pilot projects to develop and test preventive agents or therapies.

Conduct basic biological research. $7.0 M

■ Initiate prospective studies to identify genetic and biological factors affecting vulnerability to

tobacco-related cancers.

■ Fund innovative studies to determine how tobacco use contributes to non-aerodigestive cancers.

■ Develop and use a Tobacco Carcinogenesis Models forum to link Mouse Models of Human Cancer

Consortium participants to investigators with expertise in behavioral and other models of tobacco

carcinogenesis.

Expand surveillance. $3.0 M

■ Expand surveillance systems to monitor tobacco use behaviors, tobacco-related intervention,

implementation and durability, and other factors.

Enhance national research infrastructure. $20.0 M

■ Double the number of TTURCs to expand the scope of research and capitalize on new discoveries. 

■ Fund transdisciplinary research and training programs.

■ Create a NCI clinical research program on nicotine addiction and tobacco use.

Management and support. $3.0 M

TOTAL $66.0 M
Extraordinary Opportunities 69

Opportunities

Cancer Communications 6 OPPORTUNITY

THE OPPORTUNITY

We are in the midst of a communications revolution unparalleled since Gutenberg introduced movable type to the western world in the

15th century. At no other time in history has it

been so easy for so many people to access such a

vast wealth of information. In particular, the

Internet has multiplied exponentially our ability

to make large amounts of information available to

a wide audience quickly and easily.

Communication is central to effective, quality

cancer care, from primary prevention to survivorship and end of life issues. Communication

empowers people; it can raise awareness of health

problems and recommended actions, and give people the information they need to make informed

cancer-related decisions. Effective communications can move people to engage in behaviors that

will improve their health, such as stopping smoking or undergoing screening for certain types of

cancer. The Department of Health and Human

Services’ Science Panel on Interactive

Communications and Health has concluded that

few other health-related interventions have the

potential of interactive health communications 

to simultaneously improve health outcomes,

decrease health care costs, and enhance consumer

satisfaction. 

Scientists and communications experts have

been studying the process of effective communication and its impact on health for more than 25

years. They have produced increasingly refined

theories of health communication, including those

that focus on how people process health information and how they respond to cancer-related risks.

These theories have enabled us to refine messages

for people who differ in their readiness to take

responsibility for their health. For example, intervention research on effective health communications has contributed to declining smoking rates

among many groups in the U.S. Likewise, it has

influenced the increasing proportions of

Americans who are eating five fruits and vegetables per day, and getting screened for breast, cervical, and other cancers. 

Moreover, changes in the role and accessibility

of information are altering health care practices,

patient-physician relationships, and the way consumers and patients acquire and use information.

Where once physicians were the main source of

health information, now many consumers are

actively seeking information to meet their needs.

The commercial sector has responded to this paradigm shift by developing new communications

technologies at a dizzying rate. As we enter the

21st century, consumers and professionals alike

have, or will have, a host of new opportunities for

creating, distributing, and acquiring health information from the World Wide Web, individuallytailored print and multimedia materials, interactive computer games, interactive kiosks, and wireless pagers, among others. 

It is impossible to overstate the impact of these

“new media” on health communications.

Consider, for example, the fact that: 

■ In 1998, 22.3 million adults in the U.S.

searched on-line for health and medical information, and cancer was one of the most soughtafter topics. 

■ Also in 1998, 1.3 million pieces of e-mail were

processed each week by cancer-related listservs

(e-mail groups devoted to a specific topic) 

hosted by the Association of Cancer On-line

Resources. 

■ In 1997, 41 percent of U.S. households had at

least one personal computer, and that number

continues to increase.
But this new world of expanded communications capabilities remains in many ways uncharted

territory. Important questions confront us. How

can we promote the demand for, access to, and use

of cancer information, given the high national

rates of medical illiteracy? How can we ensure that

cancer communications are salient, accurate, relevant, and culturally sensitive to diverse audiences?

How can we better design our interventions to use

what works, to know what does not work, and to

understand why? How can we help physicians to

maximize their communication about cancer?

How can we redesign information systems so they

give people the information they want, how they

want it, when and where they want it?

In addition, substantial barriers prevent major

segments of the population from seeking and/or

using cancer information. Some people continue to

lack access to the medium. Others are faced with

content that is unintelligible (i.e., in the wrong

language or in language that is too complex), culturally inappropriate, or simply ineffective. 

Furthermore, despite our progress in refining

health communications theories, major gaps

remain in our understanding of how consumers use

health information. We must learn how to help

people distinguish important from insignificant

health risks and deal with contradictory health

messages so that they can make informed choices.

We must provide accurate and balanced information about all areas of cancer treatment and care,

including complementary and alternative therapies. We must find the best ways to inform doctors

of emerging “best practices” in patient care. And

we must find ways to help physicians be more

effective communicators and integrate cancer

communications into all aspects of cancer care.

Cancer communication must be used to narrow

the enormous gap between what we know and

what we do at all levels and to reduce health disparities among our people. For example, new

avenues are needed to reach children, especially

those in vulnerable, high-risk populations. NCI is

committed to improving demand for, access to,

and use of cancer information for all, regardless of

race, ethnicity, health status, education, income,

age, gender, or geographic region. 

Finally, new information technologies must

complement, not replace, older but effective strategies, such as the mass media, one-to-one counseling, and targeted print communications. We know,

for example, that many people still want to talk

with a knowledgeable and supportive person. As

we develop new technologies, we must not lose

sight of the importance of the human bond.

To be effective, cancer communications must

be integrated into the cancer continuum – from

prevention through treatment to survivorship and

to end of life issues, including palliative care and

pain management. Communication should be an

integral component of quality cancer care. NCI

and its grantees and contractors have traditionally

been leaders in health communication, but it is

time to go beyond what we have done before – to

take advantage of new knowledge about health

behavior and new technology – to reduce the burden of cancer. If NCI takes the lead now, we have

the opportunity to use both proven strategies and

new communications technologies to help people

increase their knowledge, enhance their ability to

negotiate the health care system, understand and

modify their health risk behaviors, speed the pace

of discoveries, and increase access to and participation in clinical trials. Moreover, we will have a

far richer understanding of how people use communications technologies of all kinds. Ultimately,

we will improve outcomes in cancer prevention,

early detection, treatment, and survivorship. 

By investing now, we will seize a crucial opportunity to shape the emerging national information

infrastructure to improve cancer communications.

At this pivotal juncture, there is a need for a public institution such as NCI to provide leadership

in the cancer communications arena; the broad

and reasoned perspective that NCI brings to

patients and health care providers alike is essential

to successfully implement communications strategies to reduce the cancer burden. 

70 The Nation’s Investment in Cancer Research
THE GOALS 

■ Accelerate reductions in the U.S. cancer burden through the use of cancer communications. 

■ Integrate cancer communications into the cancer continuum so that it is an accepted and

practiced component of quality care.

■ Increase the demand for, access to, and use of

cancer communications by diverse populations

including the public, high-risk persons, underserved and disabled populations, children,

patients, survivors, and health professionals. 

■ Use cancer communications to speed the dissemination of “best practices” across the cancer

continuum from prevention through treatment

and survivorship or end of life. 

■ Strengthen and monitor the use and efficacy of

NCI’s own communications and communication products. 

■ Develop the infrastructure needed to accelerate

advances in cancer communications, such as

the testing of strategies, models, and tools; and

dissemination of results to researchers, clinicians, patients, practitioners, advocacy groups,

other partners, and the public, including emerging on-line communities of interest. 

THE PLAN

Objectives

1. Establish new data collection and analysis

strategies to obtain data at regular intervals

for cancer communications planning,

research, evaluation, and marketing. 

■ Sponsor a triennial survey of a nationally representative sample of the U.S. population

that is conducted on a recurring basis with

input from investigators in the field. 

■ Add questionnaire items to the National

Health Interview Survey and the CDC

Behavioral Risk Factor Surveillance Survey

to more effectively monitor national trends

related to cancer communications.

■ Track promising new product development,

monitor software developers and hardware

manufacturers as well as market research

firms that monitor developers and manufacturers and often are the first to spot new

product uses.

■ As technology evolves, monitor emerging

information needs and ensure that mechanisms are in place to conduct the appropriate

research to address unmet and perhaps previously unarticulated needs.

Extraordinary Opportunities 71

Opportunities

Fundamental Assumptions of Cancer

Communications

■ Proactive communication strategies are needed across

the cancer continuum to rapidly accelerate a reduction

in the cancer burden and across the life span. 

■ A successful strategy requires that we reach a 

broad cross-section of the U.S. population. 

■ NCI’s cancer communications should be based on 

scientific evidence obtained through high quality

research and its products should be evaluated for 

efficacy, impact, and use by the target audiences. 

■ Access includes removing cost barriers and improving

ease of use, familiarity, cultural appropriateness, and

appeal of the medium. 

■ Comprehension is essential, and messages must be 

perceived as salient, appropriate, and relevant.

■ We must offer a flexible and adaptable menu of 

communication choices to reach the public, patients,

underserved populations, survivors, and health 

providers in diverse settings.

■ The new media should complement more “traditional”

media such as mass media, the telephone, and 

one-to-one interpersonal communications. 

■ We must forge effective partnerships with other 

NIH Institutes, the Centers for Disease Control and

Prevention, voluntary health organizations such as 

the American Cancer Society, and advocacy and 

self-help groups.

■ Partnerships with industry and academia are essential 

to identify and gain access to emerging communication

technologies. These partnerships should include 

computer, telecommunications, pharmaceutical, 

insurance, and new media companies.
2. Create Cancer Communications Centers of

Excellence to provide interdisciplinary units

for communications research. 

■ Facilitate rapid advances in knowledge about

cancer communications.

■ Develop new theories of health and cancer

communications that are appropriate to

underserved populations.

■ Develop strategies to improve the penetration, efficacy, effectiveness, and dissemination

of cancer communications.

■ Identify optimal formats for communicating

cancer risks.

3. Develop an integrated cancer knowledge 

management strategy, including an adapted

Cancer Information Service (CIS) that offers

a menu of communication choices designed to

meet and respond to people’s diverse information needs. 

■ Integrate NCI’s information services.

■ Infuse new media technologies into all NCI

information services.

■ Disseminate best processes.

■ Support and use new research methodologies

and approaches to respond to the swift pace

of change inherent in the communications

revolution.

■ Create an extended enterprise knowledge

base at NCI that integrates linkages to appropriate external resources.

■ Foster cooperative relationships with other

public health agencies, advocacy groups, support organizations, and industry.

4. Develop new communication products to

improve cancer communications to diverse

audiences.

■ Develop and update regularly practical toolkits for the public, patients and their caregivers, underserved populations, advocacy

groups, health professionals, and cancer communicators to improve the state of cancer

communications.

■ Fund research to develop practical decision

aids to improve patient-provider communication and to help people make better cancerrelated decisions.

■ Fund workshops and seminars to promote dissemination and use of these practical tools

and to solicit information concerning current

levels of use and barriers.

5. Identify, create, and nurture the newest and

most promising communication technologies. 

■ Collaborate with academia and the private

sector to encourage the development or new

uses of software and hardware to improve

cancer communications. 

6. Train the health communications scientists,

researchers, and practitioners needed to

achieve our scientific and health communications objectives. 

■ Encourage the development of interdisciplinary training programs that, at a minimum,

include people in health behavior, marketing,

engineering, communications, public health,

and medicine.

■ Fund existing health communications

research laboratories to conduct training programs and provide opportunities for research

professionals in growing areas, including risk

communication.

72 The Nation’s Investment in Cancer Research
Extraordinary Opportunities 73

Opportunities

Resources: Cancer Communications

Expand data collection. $5.0 M

■ Sponsor a nationally representative triennial survey and make results publicly available. 

■ Add questions to established surveys to monitor national trends in cancer communication.

■ Track promising new product development.

Establish 6-8 Cancer Communication Centers of Excellence. $12.0 M

Develop an integrated cancer knowledge management strategy. $10.0 M

■ Integrate new media technologies into NCI information services; link to external resources.

■ Support new research methods/approaches and disseminate best processes.

■ Integrate new information technologies for easier, more efficient, and less costly organization,

packaging, and communication of cancer information for users with diverse needs. 

■ Foster relationships with public health agencies, advocacy groups, and industry.

■ Expand communication choices available through CIS. 

■ Integrate the restructure of PDQ and the CIS activities into NCI’s clinical research program.

Develop practical tools for cancer communications. $3.5 M

■ Develop toolkits for media, public, patients, underserved populations, advocacy organizations,

health professionals, and cancer communicators to improve cancer communications.

■ Support development of decision tools, appropriate for underserved populations.

Identify, create, and support promising communications technologies. $1.5 M

■ Expand JOLT (Joining Organizations with Leading Technologies).

■ Co-sponsor state-of-the-art meetings on emerging technologies.

Foster interdisciplinary training and educational programs. $6.0 M

■ Develop interdisciplinary training programs to prepare needed personnel in cancer-related 

consumer health informatics and cancer communications. 

■ Fund existing health communications research laboratories to conduct short- or longer-format

training programs for research professionals.

■ Develop a Master’s Program in health communications and media technology delivery. 

Develop NCI infrastructure in cancer communications research. $4.0 M

■ Recruit staff expert in health communications and media development, use, and research.

■ Create an in-house laboratory for testing cancer communications. 

■ Implement freestanding science bureau to improve reporting in cancer communications.

Management and support. $1.0 M

TOTAL $43.0 M
74 The Nation’s Investment in Cancer Research

A

s we begin the 21st century, we are without

doubt in a position to make real improvements in human health and disease. We

made remarkable progress in the 20th century in

our knowledge of cancer biology, dramatically

expanding our understanding of what is required

to turn a normal cell into a cancer cell. Recently

developed molecular-based technologies are providing even greater insights into the steps

involved in the transformation of cells from 

normal to precancerous to cancerous, allowing us

to detect and diagnose cancers much earlier.

Other advances in technology, such as new and

enhanced imaging tools and techniques, coupled

with new drugs, targeted therapeutic interventions, and new insights and discoveries into the

fundamental nature and causes of cancer, present

unprecedented opportunities for advancing our

understanding of cancer and improving quality 

of life for people diagnosed with cancer.

The challenge before us is to establish the

mechanisms that will allow the scientific community to apply these discoveries and emerging 

technologies to the field of cancer research. We

need mechanisms that will promote and reward

innovative thinking, the cross-fertilization of 

ideas among disparate scientific disciplines, and

enhanced collaborations among government, 

academia, and industry. We also must develop 

and maintain the cadre of trained scientists 

from many disciplines needed to undertake this

essential work.

NCI’s role is to provide the vision, creative

environments, and diverse resources needed to

ensure a smooth flow between the increasing number of discoveries and advances in cancer research

and the scientific community’s ability to apply

these findings to prevent and treat the many forms

of cancer. Yet if the pace of discovery is like an

eight-lane highway, our current ability to translate

those discoveries into clinical application is like a

country road. Where the two meet, a bottleneck

of good ideas occurs. Our challenge is to expand

the country road to an eight-lane highway that

moves discoveries swiftly to their use in interventions across the continuum of cancer care. 

To respond to this challenge, we have identified

six key areas for investment – InvestigatorInitiated Research; Centers, Networks, and

Consortia; National Clinical Trials Program;

Informatics and Information Flow; Studying

Emerging Trends in Cancer; and Training,

Education, and Career Development. Each of

these investment areas will play a unique role in

our fight against cancer. 

NCI’s Challenge: 

Building the Capacity of the Future

Challenge Program Increase

(dollars in thousands)

Amount

Investigator-Initiated Research $ 146,015

Centers, Networks, and Consortia 62,350

National Clinical Trials Program 201,335

Informatics and Information Flow 70,000

Studying Emerging Trends in Cancer 56,600

Training, Education, and Career Development 60,700

Total $597,000
NCI’s Challenge 75

Challenges

Investigator-Initiated Research 1 CHALLENGE

THE CHALLENGE

I

nvestigator-initiated research – research proposed and conducted by scientists in laboratories and clinics across the country and here at NCI

– is the wellspring of scientific discovery. Funded

and sustained by a variety of NCI grant mechanisms, our investigator-initiated research is continually yielding discoveries and insights into the

mechanisms and causes of cancer and its prevention, detection, diagnosis, treatment, control, and

survival. These discoveries, and their application

in interventions of all kinds, are critical to reducing the burden of cancer and are resulting in real

progress against cancer. 

Through the dedicated work of these NCI-supported scientists over the past 50 years, we stand

at the threshold of understanding a great unknown

– how cancer develops at the molecular level.

Because of our continued national commitment to

cancer research, we are poised to expose more rapidly than ever before the inner workings of cancer

cells, their genes, and the ways in which they

behave. We must push forward as quickly as possible with this work. The absolute number and pace

of our discoveries, and the speed with which we

bring them to bear to benefit people, are directly

linked to the level of resources available to support the exploration of new leads across the cancer

research continuum. Moreover, we must strive to

expand our research portfolio to include a greater

number of research proposals that may be somewhat riskier, highly speculative, or pursue novel

paths. We also must continue to expand the translational research that converts basic science discoveries into practical, affordable, and effective

ways of restoring cancer patients to health and

preventing cancer throughout our population.

As we promote innovative research, we must

create mechanisms that link basic, clinical, and

population-based research with state-of-the-art

resources and technologies; promote collaborations among researchers inside and outside of cancer research; and draw into cancer-related research

scientists from allied fields such as chemistry, biology, physics, and mathematics. By bringing together researchers from allied fields, we will galvanize

the complementary knowledge these individuals

possess to most quickly answer the crucial questions in basic, clinical, population, and translational research. It is under this broad scientific

umbrella that discoveries in the 21st century 

will be made.

The Nation waits eagerly for the day when cancer is no longer a threat to health and life, when

most cancers are prevented, and when those that

occur are cured or controlled rapidly and successfully. To meet this challenge, we must fuel the

drive to discover the unknown by increasing our

support of innovative research and providing the

support needed to exploit the discoveries it yields.

Our research base should bring to bear the best of

our developing knowledge, as well as the best ideas

and technologies, to address the full spectrum of

cancer research questions – from basic research to

prevention and care. Continued investment in this

crucial aspect of the research infrastructure will

span the gap between discovery and application

and transform the processes by which we bring discoveries to the benefit of people.
76 The Nation’s Investment in Cancer Research

THE GOALS

■ Increase the rate of discovery.

■ Increase investigators’ access to state-of-the-art

resources, technologies, and infrastructures that

promote collaboration and speed the pace of

discovery.

■ Accelerate the application of discoveries to

benefit people.

THE PLAN

Objectives

1. Increase investment in research to ensure a

higher and sustainable success rate for competing grant applications. Today, NCI funds

just over 30 percent of competing grant applications through the Research Project Grant

(RPG) pool. To ensure that a greater number of

excellent ideas have the chance to be tested as

quickly as possible, we need to:

■ Fund 40 percent of competing applications,

including those that have the highest scientific merit, carry great risk but may yield

potentially greater reward, are unconventional but hold unique promise, are in areas of

extraordinary need in specific fields of investigation or model systems, or encourage new

investigators.

2. Encourage investigators to commit to careers

in cancer research and to propose more innovative and higher risk/higher reward projects. 

■ Continue to allocate the first 80 to 90 percent of available RPG funds to competing

applications that fall within conventional

merit rank order paylines.

■ Assure that applications from new investigators and applications that are particularly

innovative and high risk/high reward have a

reasonable funding rate.

3. Enhance the opportunity for outstanding

applications that fall just beyond established

paylines to receive more rapid reconsideration. 

■ Allocate up to 20 percent of available RPG

funds to award meritorious applications that

are outside conventional paylines, including

set-aside funds for Requests for Applications

(RFAs), Program Announcements (PAs), and

applications under other grant mechanisms.

■ Continue Accelerated Executive Review

(AER) to fund single project applications in

patient-oriented and basic research that are

near the payline and for which reviewer criticisms can be addressed rapidly; apply a similar

approach to other application types, such as

Program Project Grants.

4. Invest in areas that NCI consensus planning

processes (e.g., Progress Review Groups,

Extraordinary Opportunity Working Groups,

Advisory Committees) have identified as presenting special opportunity or need.

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

are meeting programmatic objectives.

■ Use as needed regular, novel, and special

award mechanisms and incentives announced

through competitions (e.g., PAs, RFAs) to

encourage investigation in particular areas.

■ Provide sufficient staff, resources, and

enhanced electronic communications to

improve information dissemination, enhance

coordination within and between initiatives,

and increase direct contact with applicants

and grantees.

5. Optimize each award to accelerate the pace of

discovery. In 1999, NCI grant awards averaged

four years in duration and were awarded 90 percent of recommended funds. This level of funding and project duration slows discovery

because fewer experiments can be conducted

and fewer patients accrued to clinical trials. 

■ Provide funding at full peer-reviewed 

recommended budget levels for up to five

years of support. 

■ Ensure that investigators have access to NCIsponsored resources, infrastructure, and technologies that facilitate discovery, both to

make progress as quickly as possible, and to

create breakthrough opportunities.

■ Set aside funds to award as administrative

supplements to current awardees whose

research is going better than expected, or

who are poised to test new ideas.

■ Expand award mechanisms that provide seed

funds and resources to pilot promising leads.
NCI’s Challenge 77

Challenges

6. Facilitate rapid movement from discovery to

application by encouraging interdisciplinary

and collaborative approaches.

■ Use established mechanisms and create novel

and special mechanisms to encourage collaborative and translational research. Broaden

the Phased Innovation Award to include an

application phase.

■ Expand administrative supplements to

encourage new collaborations that bring

together basic and clinical scientists; promote

additional interdisciplinary collaborations

and access to central resources such as data

bases, tissue banks, and animal models.

■ Foster and expand novel opportunities for

access to resources and technologies that 

promote interdisciplinary research and 

collaborations through centers, networks, 

and consortia.

■ Expand cooperative resource programs that

give investigators access to technologies and

expertise needed to move their discoveries to

application.

■ Encourage the development of information

technology tools to facilitate interdisciplinary

communication and collaboration.

■ Increase funding for collaborative research

awards such as Program Project Grants and

cooperative agreement networks in cancer

genetics, imaging, early detection, and 

other areas.

■ Expand use of exploratory grants to encourage patient- and population-based research.

PROGRESS TOWARD MEETING

THE CHALLENGE

Over the past four years, NCI has increased substantially the number of investigator-initiated

grant applications funded. In 1995, the overall

success rate for grants funded from the RPG pool

was 23 percent. In 1999, we anticipate funding

more than 1,200 new and competing grant applications from the RPG pool, for an overall success

rate of 33 percent. This increase has resulted in

and will continue to yield many research rewards,

but this improved funding level is still insufficient

to support the wealth of innovative, high quality

proposals received each year. In fact, as we attract

new researchers to the cancer problem the number

of excellent, innovative applications can only be

expected to grow. 

To encourage both the development of new

technologies and innovative approaches to specific

areas with special needs, NCI has implemented

several new or expanded mechanisms. For example, the Quick-Trials program was designed to

speed the translation of ideas to early stage clinical

trials. The Phased Innovation Award program

supports novel technology development for molecular analyses of cancer. Both programs promise to

encourage innovative approaches and increase the

speed at which discoveries are translated to clinical application. Through a special exceptions

process, NCI ensures that new investigators share

the same success rate as more established R01

applicants. In addition, the Accelerated Executive

Review process ensures rapid reconsideration of

applications ranked within a few percentile points

of the payline, especially those involving patientoriented research.
78 The Nation’s Investment in Cancer Research

Resources: Investigator-Initiated Research 

Ensure sustainable success rate for competing applications. 

■ Fund 40% of competing applications.

Encourage investigators to commit to cancer research careers and to propose 

more innovative and higher risk/higher reward projects.

■ Continue to allocate the first 80 to 90% of RPG funds to competing applications falling within

conventional merit rank order paylines.

■ Ensure reasonable funding success rate for high risk/high reward applications and a success rate

at least equal to traditional R01 grants for applications from new investigators.

Enhance opportunities for rapid reconsideration of outstanding applications 

that fall just beyond established paylines. 

■ Allocate up to 20% of RPG funds for meritorious applications outside conventional paylines.

■ Expand AER to include Program Project Grants.

Invest in areas of special opportunity or need.

■ Use regular, novel, and special award mechanisms to encourage investigation in priority areas.

■ Provide staff, resources, and enhanced electronic communications to improve information 

dissemination, enhance coordination within and between initiatives, and increase direct contact

with applicants and grantees.

Optimize awards to accelerate discovery.

■ Fund at full peer-reviewed recommended budget levels for up to 5 years of support.

■ Ensure access to NCI-sponsored resources, infrastructure, and technologies.

■ Set aside funds for administrative supplements.

■ Expand R03, R21, R33, and other awards to provide seed funds and resources.

Facilitate rapid movement from discovery to application through 

interdisciplinary and collaborative approaches.

■ Use established and novel mechanisms to encourage collaborative and translational research. 

Add application phase to R21/R33 Phased Innovation Award.

■ Expand administrative supplements to encourage collaborations and promote access to resources.

■ Expand access to resources and technologies that promote interdisciplinary research and 

collaborations through centers, networks, and consortia.

■ Expand cooperative resource programs (e.g., RAID, RAPID, CGAP, EDRN) to improve access to

technologies and expertise.

■ Encourage development of information technology tools to expedite interdisciplinary 

communication and collaboration.

■ Double funding for collaborative research awards.

■ Expand exploratory grants for patient- and population-based research.

Management and support. $2.0 M

TOTAL $146.0 M
THE CHALLENGE

The rapid pace of scientific and technological discovery has created enormous opportunities.

Along with them come some very significant challenges. The most obvious one – how to turn scientific knowledge into more effective cure and control

of cancer – is NCI’s mission. To do this most effectively, the research community must first successfully address another challenge – one having to do

with the culture of the research community itself. 

For decades, laboratory-based biological investigation – the “basic science” of cancer research –

has flourished in the familiar departments of our

medical schools, universities, and research institutes. It has always been a kind of “cottage industry” in which small, cohesive laboratory groups are

the units that do the research, sometimes working

with similar groups in ad hoc collaborations. As

biomedical science has advanced, however, it has

become clear that certain kinds of scientific problems cannot be addressed in this way. This has

long been the case for certain epidemiologic studies and clinical and populations research, which

often require teams of substantial size that may

straddle multiple institutions. What is really new,

however, is the sheer extent to which the need for

“team research” has come to pervade biology and

medicine, particularly for those problems that

require back-and-forth movement between the

laboratory and clinics or populations. 

Multidisciplinary teams are needed to solve virtually all of the “big” problems in cancer research –

sequencing the genome, creating the next generation of sensitive and specific imaging devices, or

discovering and testing target-specific therapeutics

and preventives. Increasingly, single institutions do

not have the scientific breadth, patient resources,

or regional outreach to populations to enable them

to address the major scientific questions upon

which really effective cancer control will depend.

The cultural challenge to the scientific community,

therefore, is to go beyond customary ways of thinking and organizing, beyond traditional academic

departments and faculties, to establish whatever

kinds of cross-disciplinary and multi-institutional

collaborations are needed to get the work done. 

More specifically, we need to create quite new

kinds of functional links – not only among basic,

clinical, and population scientists, but also across

very diverse fields of science and technology. We

need productive interfaces among and between

mathematicians, biologists, computer scientists,

epidemiologists, imaging scientists, chemists,

physicists, and clinicians. Similarly, as scientific

and technological development provides us with

new tools to intervene at many points along the

entire trajectory of malignancy, the actual testing

of these new interventions – whether for prevention, detection, diagnosis, or treatment – will

require the collaboration of many scientists with

diverse backgrounds. These scientists will require

access to many different kinds of resources, such as

patients, at-risk populations, tissue banks, new

technologies, and state-of-the-art informatics.

These many requirements will best be satisfied by

specialized networks, centers, and consortia that

incorporate diverse expertise and flexibility in

funding and in administration.

For these reasons, NCI proposes to expand its

programs for Centers of Research Excellence and

Cancer Centers and to develop a variety of new

research networks and consortia. Centers can serve

as platforms for developing and providing access to

technologies, for promoting and facilitating complex scientific interactions, and for providing the

critical resources essential for research studies of

great scope. NCI will enable more specialized

research networks and consortia to develop novel

capabilities and link with NCI Cancer Centers. 

NCI-designated Cancer Centers

The NCI-designated Cancer Centers are key 

partners in NCI’s efforts to speed the process of

Centers, Networks, and Consortia 2 CHALLENGE

NCI’s Challenge 79

Challenges
discovery and bring the benefits of cancer research

directly to the public. Centers coordinate multidisciplinary approaches to research questions, 

provide access to the most advanced research

technologies, and take rapid advantage of new

research opportunities. Support of the Cancer

Centers helps ensure a close association between

state-of-the-art research and clinical care activities

within the institution. It also allows each Center

to develop key collaborations and partnerships

within industrial, community, and state health

organizations, and link the research capabilities

and expertise of scientists within the institution to

problems of cancer incidence and mortality in

their communities and regions. 

Establishing partnerships between and

among NCI-supported centers and

research institutions is equally important.

NCI will create Regional Enhancement

Centers that will work closely with existing NCI-designated Comprehensive

Cancer Centers; these partnerships will

provide patients and populations with

much improved access to studies in early

detection, prevention, and therapeutic

research. NCI also has recently launched

the Special Populations Network for

Cancer Awareness Research and Training. This

initiative will develop and maintain partnerships

between scientific researchers and community

leaders from a broad range of minority and underserved populations. In addition, the Cancer

Centers will be enhanced by placing a stronger

emphasis on the need for collaborations between

the Cancer Centers, industry, and non-traditional

academic sites lying outside the orbit of cancer

research. These will enable the Centers to function more effectively as platforms for broad-based

early technology development, and ensure that

the research community can gain access to these

technologies. 

Centers of Research Excellence

Centers of Research Excellence are multidisciplinary and translational research teams focused on a

specific disease, modality, biologic process, or scientific area of particular significance. They are

awarded sizeable amounts of flexible funding to

enable them to rapidly address emerging scientific

opportunities or specific challenges. NCI’s SPORE

program (Specialized Programs of Research

Excellence) is one highly successful example of this

approach. Each SPORE group focuses on a specific

cancer site. Their goal is translational: they aim to

move discoveries and observations back and forth

among laboratory, clinic, and population settings.

Research in the SPOREs focuses on approaches for

reducing cancer incidence and mortality and

improving survival and quality of life. Recent findings from the SPORE program include the identification of several tumor suppressor gene mutations

that lead to pancreatic cancer, and the first human

gene therapy approaches for advanced prostate

cancer. NCI is supporting SPOREs in cancers of

the breast, prostate, lung, and gastrointestinal tract,

and one soon will be awarded in ovarian

cancer. We plan to expand the SPORE

program to all cancer sites; each SPORE

will continue to focus on a specific cancer. 

Additional examples of the centers of

excellence concept that we have recently

implemented or will shortly implement

include those in tobacco research, molecular and in vivo imaging, communications,

population health, and interventions

directed against molecular targets. 

Consortia and Networks

Many of the most innovative ideas emerge from

groups of scientists who link their expertise and

resources to address important questions about

human cancer. NCI has taken steps to facilitate

just this sort of complex collaborative effort. For

example, we recently established the Cancer

Genetics Network (CGN), which is dedicated to

studying inherited predisposition to cancer. The

CGN consists of eight centers and an informatics

and information technology group. It builds on

recent progress in isolating genes linked to inherited cancer and promotes the application of this

knowledge to the clinical setting. The CGN not

only will integrate discoveries into medical applications such as prevention, detection, and cancer

control, but will address psychosocial, ethical,

legal, and public health implications of inherited

cancer susceptibility. The Diagnostic Imaging

Network creates, for the first time, a multi-center

research group to systematically evaluate new

imaging technologies and their impact on cancer

management and health care outcomes. We

80 The Nation’s Investment in Cancer Research

For a list of

Cancer Centers

visit

http://www.

nci.nih.gov/

cancercenters/

centerslist.html
NCI’s Challenge 81

Challenges

expect that strong collaborative relationships will

develop between the Diagnostic Imaging Network

and industrial device manufacturers, as well as

between the imaging network and our clinical

cooperative groups that perform treatment and

prevention studies. Networks for early detection

studies and for developing better animal models of

human cancer are additional examples of specialized consortia that the NCI recently has begun.

Centers and networks actively reinforce each

other. For example, NCI recently has supported

innovative proposals from several collaborating

SPOREs to study the molecular characteristics of

breast duct carcinoma in situ and to create a common language and data bases that will pave the

way for joint studies in lung cancer prevention

and early detection.

THE GOALS

■ Refine the organizational framework of centers,

consortia, and networks to stimulate and expedite interdisciplinary collaborations.

■ Promote collaborations among and between

basic, clinical, and population scientists by providing the infrastructure to support a critical mass

of expertise and a variety of study populations. 

■ Stimulate unique forms of research that can be

conducted only by interinstitutional, interdisciplinary teams of investigators.

■ Support centers and consortia as platforms for

technology development and application.

THE PLAN

Objectives

1. Increase the number and broaden the 

geographic distribution of NCI-designated

Cancer Centers. 

■ Establish new NCI-designated Cancer Centers.

■ Award new cancer center planning grants.

2. Expand NCI Cancer Center linkages to

increase their research capabilities and 

broaden their access to populations that 

currently lack access to centers.

■ Create new Regional Enhancement Cancer

Centers that will collaborate with existing

NCI-designated Comprehensive Cancer

Centers to expand the base of patients and

populations available for early detection, prevention, and therapeutic research studies. 

■ Establish formal affiliations between cancer

centers and minority institutions to strengthen the research capabilities of minority institutions and to enable collaborative research

programs focusing on the burden of cancer in

minority groups.

■ Establish a program of competitive cancer

center supplements to foster new collaborations among centers, particularly when the

centers are competing for the same populations or patient bases or when combining

resources can address important questions

more effectively. 

3. Expand the capacities of NCI-designated

Cancer Centers to engage in newly developing

areas of research that are critical to solving

the cancer problem.

■ Establish Advanced Technology Programs in

cancer centers to enable center investigators

to access cutting-edge technology developed

in industry and to develop applications and

pilot projects to solve particular problems in

cancer research. 

4. Expand the research programs in NCI’s

Specialized Programs of Research Excellence

(SPOREs) and other Centers of Research

Excellence. 

■ Expand the scope of the SPORE program to

include all cancer sites. 

■ Create and expand Centers of Research

Excellence to support multidisciplinary and

translational research teams focused on

modalities, biological processes, or scientific

areas of particular significance.

■ Provide supplements to SPOREs and other

Centers of Research Excellence to develop

and initiate complex inter-institutional

exploratory research initiatives.

■ Support the development of an Internet platform for SPOREs to exchange research results

and to foster the communications needed for

sharing resources and conducting interSPORE collaborative research. 
5. Enhance the capacity of NCI Centers to act

as platforms for translating discoveries into

interventions.

■ Provide funding for research nurses and data

managers.

■ Develop clinical trials informatics to conform

with NCI’s Cancer Informatics Infrastructure.

■ Address regulatory issues.

PROGRESS TOWARD MEETING 

THE CHALLENGE

I

n the past year, NCI has taken a number of 

steps to strengthen and expand research support

mechanisms designed to foster multidisciplinary and

multi-institutional collaborations. These collaborations are bringing together diverse scientific disciplines across institutional boundaries, improving

access to new technologies and patient populations.

The emergence of new and improved medical

imaging technologies is an area of cancer research

that will depend on effective multidisciplinary collaboration. NCI has created In Vivo Cellular and

Molecular Imaging Centers that will provide the

infrastructure to foster the interaction and collaboration of imaging scientists with basic biologists,

chemists, immunologists, computer scientists, and

physicists to focus imaging research on the detection of genotypic and phenotypic abnormalities in

oncology. Similarly, NCI is providing support for

the Diagnostic Imaging Network to bring together imaging experts from across the country to perform a broad spectrum of multi-institutional clinical diagnostic imaging trials related to cancer. 

Increasingly, tobacco control and addiction

research must rely upon scientists with expertise in

diverse areas including molecular biology, genetics,

neuroscience, epidemiology, imaging, behavioral

science, primary care, and communication. To further transdisciplinary research in tobacco control

and addiction research, NCI and the National

Institute on Drug Abuse have created Transdisciplinary Tobacco Use Research Centers. 

Two areas of extraordinary opportunity identified by NCI in this document are Defining the

Signatures of Cancer Cells: Detection and

Diagnosis, and Molecular Targets of Prevention

and Treatment. Possibly no other opportunities

challenge us to work more collaboratively in

multi-institutional settings with multidisciplinary

teams than these. As stated in the Extraordinary

Opportunities section, new molecular-based technologies are enabling us to identify features of cells

and the transformation of normal cells to cancerous cells in unprecedented ways. The implications

of these discoveries for cancer detection, diagnosis,

and treatment are profound. The NCI-supported

Early Detection Research Network (EDRN), a

multi-institutional network, links centers of

expertise in tumor biology, diagnostic technologies, and clinical trials methodology in academia

and industry to develop, evaluate, and validate

biomarkers for early cancer detection. 

To develop and test target-based therapeutics

and preventives, NCI will create a series of multidisciplinary research groups, each organized

around a mechanism of particular relevance to

cancer therapy, such as angiogenesis, cell cycle

control, immunotherapy, DNA repair, metastasis,

and apoptosis. These consortia will bring together

chemists, biologists, pharmacologists, imagers, clinicians, and informatics experts to create tools

such as assays, probes, and reagents necessary to

assess the effects of cancer drugs on their molecular targets in patients with cancer. 

Developing experimental models that mimic

the wide variety of human cancers is critical to

understanding how a cancer gene disrupts the normal processes of a cell. The challenge has always

been the lack of infrastructure to develop and distribute efficiently to the research community the

range of models necessary to represent human cancer and to validate these as predictive models of

human cancer. NCI has undertaken a major effort

to overcome these challenges by creating the

Mouse Models of Human Cancer Consortium, a

consortium of scientific laboratories and teams of

scientists dedicated to developing, validating, and

characterizing mouse models of human cancer. 

Other recently established or expanded NCIsponsored consortia include the Pediatric Brain

Tumor Consortium, a network of medical centers

that will evaluate promising treatments for children with brain malignancies; and the Community Clinical Oncology Program and the

Minority-Based Community Clinical Oncology

Program, which provide the infrastructure to link

community cancer specialists and primary care

physicians with NCI’s Clinical Cooperative

Groups and Cancer Centers. 

82 The Nation’s Investment in Cancer Research
NCI’s Challenge 83

Challenges

Resources: Centers, Networks, and Consortia 

Broaden geographic distribution of NCI-designated Cancer Centers. $5.1 M

■ Designate 3 new Cancer Centers.

■ Award 3 new Cancer Center Planning Grants.

Link NCI Cancer Centers to populations. $9.5 M

■ Establish 2 Regional Enhancement Cancer Centers.

■ Establish formal affiliations between NCI Cancer Centers and minority institutions.

■ Award Cancer Center supplements to support inter-center collaborations.

Expand capacity of NCI-designated Cancer Centers. $16.0 M

■ Establish 10 Advanced Technology Programs in Cancer Centers.

Expand NCI’s Specialized Programs of Research Excellence (SPOREs) and 

other Centers of Research Excellence. $15.3 M

■ Establish 6 new SPOREs/Centers of Excellence.

■ Provide supplements to SPOREs and Centers of Research Excellence for inter-institutional

exploratory research initiatives.

■ Support development of Internet platform for SPOREs.

■ Support Centers of Research Excellence.1

Enhance capacity of NCI Centers to act as platforms for translating discoveries 

into interventions. $14.5 M

■ Provide funding for research nurses and data managers.

■ Develop clinical trials informatics to conform with NCI’s CII.

■ Address regulatory issues.

Management and support. $2.0 M

TOTAL $62.4 M 

1 See Cancer Imaging, Molecular Targets for Prevention and Treatment, Research on 

Tobacco and Tobacco-Related Cancers, Cancer Communications, and Studying Emerging 

Trends in Cancer for specific budget items.
THE CHALLENGE

The research investment of the past decade has

produced major advances in our understanding

of tumor biology and molecular targets – the

tumor-related molecules that can be selectively targeted to treat or prevent cancer. It also has brought

about a dramatic increase in the number of new

preventive, diagnostic, and therapeutic agents

being tested in clinical trials. But our present clinical trials system is failing to keep pace with the

growing number of agents that will merit testing in

people. Currently, an estimated 354 new cancer

treatments are in development by industry, a threefold increase during the 1990s. In 1999, NCI

entered into clinical trials approximately 30 novel

agents discovered through its own drug discovery

programs or in collaboration with academic institutions or industry. This is in addition to 78 promising new interventions for treatment and 32 for prevention that NCI already is testing in people.

As these potential treatments and prevention

strategies emerge from early clinical testing, NCI is

faced with a backlog of agents that need to enter

large Phase III trials – the final crucial step in the

translation of new discoveries into effective new

treatments and prevention strategies for patients.

(See page 27 for more information.) At present,

NCI and its grantees are able to initiate only about

30 Phase III trials each year. Compounding this

3 National Clinical Trials Program

CHALLENGE

84 The Nation’s Investment in Cancer Research

Without question, our ability to prevent cervical

cancer through regular Papanicolaou screening

tests – also called the Pap smear – is a major public

health success story in the United States and many

other countries with established screening programs.

But in developing countries, few women receive this

life-saving screening, and invasive cervical cancer still

strikes an estimated 350,000 women each year, killing

200,000. And even with the success of cervical cancer

screening in the U.S., about 15,000 women each year

will learn that they have this disease. Some older

women fail to be screened because they believe they are

no longer at risk, or because their physicians do not

recommend screening. HIV-positive women, whose

immune systems are weakened, are at greater risk of

infection with the human papillomavirus (HPV) that has

been discovered to be the primary cause of 90 percent

of cervical cancers. In addition, some populations of

women still avoid screening, or live in medically underserved areas where screening rates are as low as those

in developing nations. For these reasons, population,

laboratory, and clinical researchers are working to discover more effective, less invasive, and less costly ways

to prevent, diagnose, and treat cervical cancer here and

around the world.

Population and laboratory studies led to discovery of the

HPV-cervical cancer link, and clinical studies have shown

that while sexually transmitted HPV infection is widespread in the population, most infections go away by

themselves within six months. Moreover, we now know

that only a small percentage of women with HPV – even

those infected with the HPV types most associated with

cervical cancer – actually develop the disease. Further,

even moderately severe cell proliferation believed to be a

precursor of invasive cancer may regress spontaneously,

suggesting new approaches to monitoring and treating

these early lesions.

SPOTLIGHT ON RESEARCH

Viruses, Vinegar, and Vaccines – 

Preventing Cervical Cancer
NCI’s Challenge 85

Challenges

problem is the fact that for a variety of reasons –

e.g., limited access, lack of insurance coverage,

patient-physician communication issues, therapy

choice – only about 20,000 patients enter Phase III

trials each year. Overall, fewer than three percent

of patients with cancer participate in the clinical

trials that define effective new treatment

approaches. Thus, it can take over four years just to

recruit enough patients for the average Phase III

trial. In addition, more than 80 Phase II and III

prevention trials have been initiated, but progress

in this area is limited by lack of methods, such as

biomarkers, to determine the effect of a preventive

over a short period of time, lack of technologies to

improve precision in characterizing precancerous

lesions, and the growing number and complexity of

trials needed to determine the roles of this new

generation of agents. 

How can we more efficiently convert recent scientific discoveries into effective interventions,

eliminate the backlog of agents for testing, and

increase patient access? We must invest in, restructure, and increase the capacity of our national clinical trials program. NCI has reconfigured major

aspects of its clinical trials program to increase the

speed and smooth the path for entering promising

agents into trials. While the time from initiation of

clinical trials to Food and Drug Administration

(FDA) approval has improved over the past

decade, the clinical development required to establish the best uses of new agents still occurs over a

much longer period. For example, paclitaxel

(Taxol®), approved for use in ovarian cancer in

1992, also has a potentially life-saving role in several other cancers, including cancers of the breast,

lung, prostate, head and neck, esophagus, and bladder. Even so, the clinical trials to define its use in

these diseases are still ongoing seven years after

FDA approval for ovarian cancer treatment. 

The changes we propose in the following plan

will substantially increase the number of trials and

number of patients who enroll in trials each year

by easing the way for physicians to communicate

with patients and enroll them in clinical trials.

The plan also calls for funding the kinds of laboratory studies that will help determine why particular

These and other findings are leading to much-needed interventions for women. A refined Pap test is slowly gaining

acceptance in community practice; more cells are sampled,

cell preparation errors are less likely, and the sample can be

saved and reused if a reading is questionable. The new test

also is easier to read and substantially more accurate. In

developing nations, an easily performed screening test in

which the cervix is swabbed with a vinegar solution that

discolors only abnormal cells is being studied in selected

populations. It could bring affordable screening to millions

of women in countries where health care resources and personnel are so scarce that currently, only five percent of

women are screened for cervical cancer. HPV DNA testing

for women who have a questionable Pap smear shows promise as a reliable, less invasive, and less costly method of

determining a woman’s cervical cancer risk and catching

early disease, compared with current approaches.

Prevention vaccines are being developed that will prime the

immune system to recognize both cancer-linked and other

HPV types and attack if infection occurs. If given to men

as well as women, these vaccines will prevent cervical cancer and also may prevent sexually transmitted HPV diseases

like genital warts that affect both genders.

There also is encouraging news for women who do develop

suspicious cervical dysplasia or invasive cervical cancer. To

better guide the treatment of precancerous cervical

changes, a refined and simplified system of classifying

these early lesions – the Bethesda system – has been

established. Treatment vaccines that spur the immune system to attack existing HPV infection are on the near horizon. Of great importance, NCI recently issued a special

announcement to physicians to inform them of the results

of five clinical trials involving women with locally and

regionally advanced cervical cancer. These trials showed

that women achieved significantly improved survival when

cisplatin-based chemotherapy was given concurrently with

radiation therapy – the risk of cervical cancer death was

reduced by 30 percent. Based on these definitive results,

NCI strongly urges that physicians consider adding

chemotherapy to the treatment of women who require

radiation therapy for cervical cancer.
86 The Nation’s Investment in Cancer Research

drugs are effective in some patients and not in others. The results will help us tailor treatments for

cancer patients in the future. These enhancements

will help speed development of agents and alleviate the backlog of agents awaiting evaluation.

THE GOALS

■ Create a more effective and efficient clinical

trials system.

■ Accelerate clinical evaluation of the best scientific ideas and approaches for treatment and

prevention.

■ Study a broader range of clinically relevant

questions.

■ Enhance collaborations between NCI, academia,

industry, and other agencies in developing promising therapeutic and preventive approaches.

■ Make access to clinical trials a realistic 

possibility for many more patients with cancer.

■ Achieve better short-term assessment of promising strategies by developing and validating

molecular and imaging risk biomarkers.

THE PLAN

Objectives

1. Increase pace of development and clinical testing for new therapeutic and preventive agents.

■ Triple the number of promising agents entering Phase I and II clinical trials annually. 

■ Implement a new rapid-review grant support

program for mechanism-based clinical trials

(Quick-Trials) to support trials of novel

agents and the associated laboratory studies

that assess a drug’s effects on its target.

■ Include correlative laboratory studies in clinical trials to elucidate the molecular mechanisms of response and drug effects.

2. Address compelling clinical questions 

confronting physicians and patients 

struggling with cancer.

■ Conduct disease-specific State of the Science

Meetings to bring together the Nation’s leading

multidisciplinary experts, to identify the important research questions for a given disease and

help define the scientific research agenda that

will assist us in addressing those questions.

■ Sponsor clinical trials of the best scientific

concepts from individual academic sites or

investigators, pharmaceutical or biotechnology companies, or others through NCI’s

national network of cooperative groups and

community practice sites.

■ Provide Concept Evaluation Panels for NCI

Phase III trials conducted through our

national accrual network 

■ Provide scientific leadership funding to permit

academic investigators the time necessary to

develop and conduct clinical research protocols.

■ Provide funds for correlative studies to 

elucidate the mechanisms underlying new

treatments and preventive strategies.

■ Support the broad acquisition of tumor 

specimens/tumor banks to facilitate rapid

evaluation of new assays and relevant clinical

correlations as new targets are identified.

■ Use Centers of Excellence to develop the

molecular assays required to characterize/

classify patient tumors.

■ Develop reference laboratories so that 

appropriate assays are widely available.

3. Maximize the use of existing clinical trials infrastructure to study prevention and treatment outcomes and other clinically relevant questions.

■ Integrate treatment with prevention, early

detection, epidemiology, behavioral, and

other relevant research areas to most effectively address the burden of cancer in specific

tumor types and patient populations.

4. Develop common informatics systems, shared

data bases, and information resources that

allow physicians to enroll patients in trials

and report data from any site nationwide.

■ Establish common data elements so that 

all clinical trials are written in the same 

“language” and so that results can be easily

combined and compared.

■ Develop common forms and interfaces for

physicians participating in trials.

■ Create electronic protocol authoring tools to

speed protocol generation.

■ Create electronic update and reporting systems.

5. Increase the number of referring physicians

and patients who participate in clinical trials.

■ Create a national accrual network that allows

physicians to enroll patients in any of the

Phase III trials sponsored by NCI.
■ Extend outreach efforts to physicians in busy

and competitive practice settings; provide the

data management and research support they

need to enroll their patients on clinical trials.

■ Extend outreach to minority patients and

physicians to improve their access to state-ofthe-art cancer therapy. 

■ Use a variety of media to increase substantially the information available to patients about

clinical trials.

■ Provide extensive electronic information

about available treatment and prevention

protocols to physicians.

6. Create collaborations to optimize resources.

■ Facilitate new partnerships with academia, industry, patient advocacy

groups, professional societies, and

other organizations to accomplish

research objectives, share resources,

and avoid duplication.

■ Provide opportunities for industry to

invest in and use the national clinical trials infrastructure to perform

important clinical trials.

7. Identify relevant biomarkers.

■ Identify novel response-related biomarkers by measuring tumor burden.

■ Conduct research on molecular profiling of

cancer cells to identify patients most

likely to benefit from specific treatments. Monitoring biomarkers can

more quickly identify patients with a

suboptimal response who may require

a change or discontinuation of treatment.

■ Fund intergroup studies to evaluate

biomarkers for monitoring treatment

response.

8. Support intramural clinical trials.

■ Support high priority clinical trials

conducted at the NIH Clinical

Center.

PROGRESS TOWARD MEETING 

THE CHALLENGE

I

n 1996, an external review group conducted an

in-depth review of NCI’s clinical trials system. The review group made major recommendations regarding review, funding, design, oversight,

and administration of our clinical trials system. In

September 1998, a plan for implementing these

recommendations was approved. Since that time a

number of pilot projects have been initiated:

■ State of the Science Meetings are being held on

prostate cancer (November 1999 and February

2000), lung cancer (September 1999), leukemia

(March and September 2000), and colorectal

cancer (January 2000).

■ This year, Concept Evaluation Panels, expert

panels of nationally renowned scientists, 

were formed to review and prioritize Phase III

clinical trials proposals in lung and genitourinary cancers.

■ A Cancer Trials Support Unit (CTSU)

was created to centralize administrative

and data management functions now

duplicated in numerous clinical trials

organizations. A Request for Proposals

was issued in March 1999 with awards

planned for September 1999.

■ New Cooperative Group peer review

criteria and procedures were implemented in March 1999.

Along with the launch of several new pilot

projects, NCI has increased funding for its

Cooperative Groups (see page 28), which

have been funded below peer review recommended levels for many years. A 29

percent increase in funding was provided

in 1999, reducing the gap in funding by

33 percent overall.

Finally, we are implementing new

information systems, such as an electronic Adverse Event Reporting System that

captures information on severe toxicities

experienced on clinical trials, and a

Physician Communication Module in collaboration with the Howard University

Cancer Center. This computer-based tool

will facilitate clinical trials data collection, help physicians in office settings

identify trials for eligible patients, and

provide educational information. This

project should increase minority physician

and patient participation in NCI clinical trials. 

NCI’s Challenge 87

Challenges

For more 

information on

the clinical trials

review visit

http://ctep.

info.nih.gov/

Armitage/

For more 

information on

clinical trials

implementation

visit 

http://

cancertrials.

nci.nih.gov/

NCI_CANCER_

TRIALS/zones/

Tools/Booklets/

Plan/index.

html
88 The Nation’s Investment in Cancer Research

Accelerate new agent development and clinical testing. $121.8 M

■ Increase funding for Early Therapeutics Development contracts.

■ Implement Quick-Trials.

■ Establish Centers of Excellence in interventions directed to molecular targets.

■ Establish Translational Research Fund for correlative laboratory studies in clinical trials.

■ Establish Group Developmental Fund to support Cooperative Group pilot correlative studies.

■ Provide adequate funding to Cooperative Groups and practice sites for data management 

and to double or triple physician participation in clinical trials.

■ Provide information about treatment and prevention options and clinical trials needed to 

enable patients and physicians to make informed treatment choices. (See Informatics)

■ Increase contracts for prevention drug development; accelerate patient accrual to prevention trials.

Address the most compelling clinical questions. $31.6 M

■ Conduct State of the Science meetings for genitourinary and lung cancers.

■ Establish Concept Evaluation Panels for NCI Phase III trials.

■ Provide Scientific Leadership Funds to study chairs and statisticians who write, monitor, and 

analyze high priority Phase III trials approved for conduct in the national accrual network.

■ Fund correlative studies to elucidate and translate basic biology from bench to bedside.

■ Fund tissue banks to store tissues from patients in studies of drug effects, molecular abnormalities 

in tumor and normal tissue, and tumor initiation and progression mechanisms.

Maximize use of existing infrastructure. $5.0 M

■ Conduct multidisciplinary meetings to explore possible Cooperative Group studies.

■ Involve multidisciplinary planning teams from NCI Divisions in State of the Science meetings. 

■ Increase the number of CCOPs to increase prevention clinical trials capacity.

Develop common informatics systems, shared data bases, and resources. $.0 M

(Budgeted in the Informatics Challenge.)

Increase number of physicians and patients participating in clinical trials. $9.0 M

■ Expand Participation Project to enable new participating physicians, including new minority

physicians, to hire the necessary research nurses and data managers.

■ Establish CTSUs to consolidate administrative tasks associated with conducting clinical trials.

■ Use Physician Communication Module to provide protocol and patient education information.

Create effective collaborations.

■ Encourage pharmaceutical/biotechnology industry to submit concepts for high priority 

Phase III trials to Concept Evaluation Panels; conduct trials through the national accrual 

network; and invest in CTSUs to reduce administrative redundancy. 

■ Encourage private foundations and other government agencies to co-fund clinical trials.

Identify relevant biomarkers. $3.0 M

■ Identify novel response-related biomarkers.

■ Conduct research on molecular profiling of cancer cells to predict treatment response. 

■ Fund intergroup studies to evaluate biomarkers of treatment.

Support intramural clinical trials. $25.0 M

■ Support high priority clinical trials conducted at the NIH Clinical Center.

Management and support. $6.0 M

TOTAL $201.4 M

Resources: National Clinical Trials Program 
NCI’s Challenge 89

Challenges

Informatics and Information Flow 4 CHALLENGE

THE CHALLENGE 

Around the globe, cancer researchers are benefitting from advances in computing and

telecommunications that, coupled with the explosive growth of the World Wide Web, help make

unprecedented research opportunities possible. As

never before, these advances in technology enable

scientists to collaborate and to generate incredible

amounts of information – the raw data from which

knowledge is created. But vast amounts of knowledge that already exist often go unused due to an

inability to access and organize information from

diverse sources. Therefore, we must ask ourselves,

how do we best collect, manage, and share this

information? 

The answer to this question lies in knowledge

management – in designing a framework to help

capture, analyze, apply, and reuse knowledge to

make possible faster, smarter, and better applications. This framework will serve as a tool to create

an interface among the research communities –

basic, translational, clinical, and population-based –

that participate in the research discovery process.

NCI is addressing the challenges presented by the

revolution in electronic communications and computing by developing a knowledge management system – a Cancer Informatics Infrastructure (CII) –

that will unify these research communities.

Employing knowledge management will reduce

drastically the time and effort needed to create and

use existing or new information, making research

discoveries possible at a scientist’s desk, in addition

to the lab. By speeding the discovery process and

translation of the best discoveries into clinical

interventions, the CII will transform cancer care

through more effective and efficient information

exchanges among all involved in cancer research.

Finally, a knowledge management system will create

new synergies within and among the fields of

research described in this document, resulting in a

dramatic acceleration of our progress against cancer. 

The first step being taken by the CII project is

developing a knowledge management system to

increase the speed with which we carry out clinical trials in cancer prevention, diagnosis, and

treatment. We are revising our criteria and standards for reporting all data collected during a clinical trial, and are developing common forms, terminology, and reporting requirements across all

types of clinical trials. This uniformity will

increase the speed, efficiency, and accuracy of

results reporting. Special data bases of medical and

scientific terminology will help researchers, clinicians, and other users of NCI information systems

to find and understand the information they seek.

The accomplishments achieved in developing

these common definitions can be applied to all

areas of the research discovery process to accelerate scientific discovery. Once in place, the components of the clinical trials knowledge management

system will be applied in the basic, translational,

and population-based research fields to manage

information and share knowledge within and

among these communities.

By investing in the CII and its broad publicprivate partnerships, we have the opportunity to

fundamentally improve our clinical trials system

and establish an infrastructure that supports comprehensive knowledge management across diverse

research disciplines. NCI’s leadership in this area

will enable us to establish a national clinical trials

effort that realizes maximum benefit from the

information revolution through increased patient

accrual, common reporting practices, and greater

sharing of knowledge with the public and the

research community. We must work quickly to

establish this infrastructure, however, as industrial

and academic institutions are investing individually in automated systems to speed discovery, lower

costs, and capture data electronically. As individual

systems are established, it will become increasingly

difficult, and eventually impossible, to institute a

common knowledge management system. The CII
will help us address the issue of compatibility,

enable us to manage the explosive growth in fundamental discoveries, and help alleviate the serious

bottleneck that exists between discovery and its

application for the benefit of patients with cancer.

THE GOALS

■ Create a common infrastructure that enables

cancer research through enhanced information

and resource exchange among researchers, clinicians, and the public. 

■ Reduce the barriers experienced by patients,

survivors, families, at-risk individuals, and

physicians seeking information about cancer

prevention, diagnosis, and treatment.

THE PLAN

Objectives

1. Design an information infrastructure and

enhance information exchange to accelerate

administration of the full range of clinical

research activities.

■ Develop a comprehensive clinical trials informatics infrastructure that ensures data compatibility and access, enhances clinical trials

recruitment, and promotes scientific knowledge exchange among all participants.

■ Develop an electronic Protocol Authoring

Toolbox that contains clinical trials “building

blocks,” including a comprehensive set of

clinical trials templates, to reduce the time

needed to create a new protocol.

■ Develop a common, on-line protocol review

process for all clinical trials that will “shepherd” approved concepts through the approval

process within three months of submittal.

2. Ensure widespread availability of all types 

of cancer information.

■ Create a usable, comprehensive cancer 

information system for the public using the

PDQ redesign as a model. 

■ Encourage voluntary electronic submission of

information on non-NCI sponsored clinical

trials to PDQ.

■ Streamline and automate research results and

clinical trials information management.

3. Extend the informatics infrastructure developed for clinical trials to basic, translational,

and population research.

■ Apply the information gained and processes

used to achieve common data definitions to

the areas of extraordinary opportunity.

■ Create mechanisms that foster interaction

between the public and private sectors for

joint development of these informatics infrastructures and knowledge exchanges across

the cancer research discovery enterprise.

4. Create a knowledge management system for

cancer research information and resources.

■ Establish an NCI-wide approach to knowledge management encompassing the wide

array of scientific and resource-related information generated through NCI research. 

■ Develop an inventory of research tools to

publicize and enhance the accessibility of scientific tools and technologies developed by

NCI that are useful and available to the

broader scientific community.

■ Develop a document management/workflow

approach that streamlines the review and

award process and portfolio management of

all funding mechanisms.

■ Provide necessary staffing and contract support to establish the labor infrastructure necessary to accomplish the stated objectives.

PROGRESS TOWARD MEETING

THE CHALLENGE

The CII project already is developing several

computer-based components of its clinical trials knowledge management system to help capture, analyze, apply, and reuse knowledge generated through clinical trials. Components designed to

help capture and manage data include:

■ Clinical Trials Informatics System. Developed

by NCI, this system provides point-of-care data

collection, document management, and digital

document capabilities. It links all phases of the

clinical trial life cycle, from protocol development, patient recruitment and screening, and

protocol implementation to publication of 

trial results.

90 The Nation’s Investment in Cancer Research
Resources: Informatics and Information Flow

Accelerate the full range of cancer research activities via enhanced $25.0 M

information exchange across a common infrastructure. 

■ Complete data models of the Common Data Elements for interventional and cancer control trials

in breast, prostate, lung, gastrointestinal, and gynecologic cancers.

■ Use Common Data Elements in all NCI-sponsored clinical trials by cooperative groups, 

cancer centers, and the FDA.

■ Implement a Protocol Authoring Toolbox to reduce time needed to create a new protocol. 

■ Increase the number of on-line protocol submissions.

■ Implement an on-line review and approval process for electronically submitted protocols.

Ensure widespread availability of all types of cancer information. $20.0 M

■ Implement the user-friendly version of PDQ.

■ Submit at least 80% of non NCI-sponsored trials on-line to PDQ.

■ Implement the comprehensive cancer information system.

Extend informatics infrastructures developed for clinical trials to basic, 

translational, and population research. $15.0 M

■ Extend data models and definitions for clinical trials to genomics, molecular targets, and 

preclinical models of cancer.

■ Implement 2 Research Partnership Platforms that use the CII for knowledge management.

Create a knowledge management system for cancer research information 

and research resources. $7.0 M

■ Implement an automated application and portfolio management system. 

■ Publish an inventory of research tools. 

Management and support. $3.0 M

TOTAL $70.0 M

■ Clinical Data Update System (CDUS). This

system achieves rapid, accurate, and secure capture of clinical trial data with minimal effort.

CDUS successfully captures the majority of trial

data within hours of submission – a process that

previously took months. 

■ Common Toxicity Criteria Interactive

Application (CTC-IA). This application identifies and grades adverse events experienced on

clinical trials. An application is being developed to capture toxicity data at the patient’s

bedside to minimize errors and duplication.

■ Adverse Events Reporting System. This system complements the CTC-IA and collects

information on severe toxicities experienced on

clinical trials to assure future patient safety.

■ Clinical Trials Monitoring Branch Audit

Information System. This system assists NCI

and cancer researchers in ensuring the quality

and scientific integrity of NCI-sponsored trials.

Additional CII components facilitate the protocol submission and approval process for clinical

trials and help pharmacists manage, order, and

track NCI investigational agents. Finally, we are

creating common data elements that will simplify

and standardize data collection for cancer trials.

NCI is also redesigning the Physician Data

Query (PDQ) – its comprehensive cancer information data base – based on substantial usability testing to make the information in it more accessible

and easier to navigate for all users. The new PDQ

Universal Database stores any type of cancer-related information – images, sound, movies, and text

– and delivers data in a wide variety of media.

NCI’s Challenge 91

Challenges
THE CHALLENGE 

Cancer surveillance – identifying and tracking

trends in our national cancer burden, and

monitoring the factors that influence these

changes – is a crucial underpinning of our efforts

to prevent and control cancer. Unequivocally, we

are making real progress against cancer, and reduction in the cancer burden on people is a critical

measure of that progress. Between 1990 and 1996,

cancer incidence and death rates dropped for all

cancers combined and for most of the top 10 cancer sites, reversing a decades-long trend of rising

cancer incidence and death in the United States.

These decreases are hard evidence of the wisdom

of this Nation’s investment in cancer research. 

Appropriate decision making in science and in public health depends on

accurate, reliable information about the

incidence and impact of disease.

Established in 1973, NCI’s Surveillance,

Epidemiology, and End Results (SEER)

cancer registry program has been a world

model for tracking population trends in

cancer morbidity and mortality The NCI

cancer surveillance program uses SEER

data to identify and study trends, track

the impact of cancer on the general population,

and provide information that researchers need to

ask critical questions about why certain populations are affected by cancer more severely than

others. SEER data have enabled us to identify

environmental carcinogens, track cancer-related

effects of tobacco on men and women, identify

geographic areas with higher than average cancer

rates, study patterns and outcomes of cancer care,

and identify risk groups for research and public

health intervention programs.

Recent changes in health care financing and

delivery, the revolution in informatics and computer programming technology, and the social and

cultural diversity of our country present new challenges and opportunities in surveillance research.

Currently, our understanding about how risk factors, screening, and treatment may affect trends in

the cancer burden is limited, and advancing our

knowledge in these areas will require new data

sources and statistical methods. To more fully

assess the Nation’s cancer burden, we need data

on patterns of care and quality of life outcomes, in

addition to the incidence, survival, and mortality

data now collected. Research is needed to improve

methods for measuring quality of life, quality of

care, health status, morbidity, family history, cancer risk behaviors, screening, and treatment as

well as methods and models for relating variables

and predicting outcomes. In addition, new investments are required to support the adoption of

methodologic tools that will improve the

precision and expand the reach of our

cancer surveillance efforts. These tools

include geographic information systems

that allow data linkage by geographic

location, new approaches to modeling

trends, and more refined cancer maps for

assembling, analyzing, and disseminating

cancer surveillance data. 

NCI’s surveillance efforts should be

expanded to cover a broader spectrum of

the racial, ethnic, socioeconomic, and cultural

diversity of our country. For example, certain

minorities and medically underserved populations

are not fully represented in SEER registries; these

groups include American Indian and Alaskan

Natives, rural whites and African Americans, and

Hispanics of Caribbean origin. New investments in

surveillance research on specific population groups

such as these will make it possible to connect

information on prevention, risk factors, screening,

treatments, and patterns of care with outcomes

such as incidence, quality of life, and survival. 

Greater efforts are needed to disseminate the

results of NCI’s surveillance research to policy

makers, advocacy groups, and the general public.

5 Studying Emerging Trends in Cancer

CHALLENGE

92 The Nation’s Investment in Cancer Research

For more 

information on

SEER visit

http://www.

seer.ims.nci.

nih.gov/
NCI’s Challenge 93

Challenges

In addition, we must improve our ability to provide epidemiologists and other population-based

investigators with the information crucial to

developing new ideas for research on cancer’s

causes and developing interventions based on

study findings. As the field of surveillance research

expands and takes on these new challenges, it is

clear that scientists with skills that encompass the

disciplines of epidemiology, statistics, disease registration, geographic information systems, and informatics are in short supply. To strengthen this

maturing scientific discipline and ensure that we

have the data we need to guide cancer research

activities of all types, we must create the training

opportunities necessary to prepare the next generation of surveillance researchers. Finally, enhancing our investment in surveillance research will

ensure that NCI continues to play an active and

visible national leadership role in developing a

comprehensive national surveillance program.

THE GOALS

■ Improve our ability to describe the cancer burden across a broader spectrum of the population,

track changes in cancer rates, and explain

observed changes in trends by their relationships

to changes in risk factor and screening data.

■ Enhance the value of the surveillance system as

a research resource by including treatment

measures and genetic studies.

■ Improve and expand communications relating

to cancer surveillance and trends to researchers,

public health professionals, advocates, legislators, policy makers, and the public.

■ Ensure a cadre of skilled surveillance researchers. 

■ Foster interdisciplinary studies within the 

population-based sciences to increase opportunities for applying new discoveries to improve

public health.

THE PLAN 

Objectives

1. Expand studies to improve our understanding

of the experience of cancer survivors, including patterns of care people receive, quality of

life they experience during and after treatment, and influence of various modes of

health services delivery on their outcomes. 

■ Support initiatives to expand patterns of care

and outcome studies among cohorts of

patients with specific types of cancer.

■ Initiate prospective cohort studies to monitor

community practice patterns for screening,

diagnosis, treatment, and health-related outcomes of men with prostate cancer.

■ Fully develop and staff a program in cancer

outcomes research.

■ Develop the infrastructure needed to collaborate with our national partners in cancer surveillance to find better ways to measure cancer care quality across all populations.

2. Improve our ability to connect data on cancer

risk factors (i.e., lifestyle behaviors and environmental exposures) and screening practices

with cancer outcomes in defined populations

with high quality cancer registration systems. 

■ Expand the Breast Cancer Surveillance

Consortium.

■ Support a Colorectal Cancer Surveillance

Consortium.

■ Support initiatives for continuing methodologic linking studies.

3. Expand SEER data collection to include 

underrepresented U.S. population segments,

including rural whites, rural African

Americans, Hispanics of Caribbean origin,

Alaskan Natives and American Indians. 

■ Support feasibility studies for adding two to

five new SEER areas (e.g., states, regions);

provide technical assistance/quality control

for seven to 21 non-SEER regions to enable

them to meet national registry standards.

■ Fund selected high quality, non-SEER registries for special surveillance studies.

4. Create opportunities to develop and share

methodologic tools for assessing, analyzing,

and disseminating data. 

■ Support studies of modeling methods.

■ Accelerate in-house development of measures

of risk and screening for surveillance.

■ Support studies incorporating geographic

information system methods for surveillance.

■ Support initiatives to develop new maps of

the cancer burden and its determinants. 
5. Enhance the SEER program by initiating the

collection of family history data and biologic

specimens from cancer patients, and by incorporating new mechanisms that allow investigators to rapidly identify new cancer patients. 

■ Support feasibility studies for collecting

biospecimens and assessing the U.S. prevalence of major familial cancers.

■ Support activities to expand the use of rapid

case ascertainment methods. 

6. Develop new informatics initiatives for surveillance data on cancer patients to be collected and disseminated rapidly but confidentially. 

■ Support pilot informatics systems.

7. Improve the dissemination of NCI’s surveillance research results to researchers, policy

makers, advocacy groups, and the public. 

■ Produce an annual “report card” to improve

dissemination of data on the cancer

burden.

■ Develop mechanisms to make surveillance information more readily

available to the academic research

community and more compelling to

the public.

■ Increase development and dissemination of surveillance data bases for

cancer research.

■ Make new products available (e.g.,

cancer maps).

8. Create cancer surveillance research

training opportunities to support the growing

need for skilled scientists with expertise in epidemiology, statistics, disease registration, geographic information systems, and informatics. 

■ Develop and fund training programs for a

new generation of surveillance researchers.

9. Create and support Centers of Excellence for

interdisciplinary studies in population-based

sciences to move basic cancer research findings into population research and increase

opportunities for applying discoveries to

improve public health.

■ Support an initiative to create Centers for

Population Health to integrate epidemiologic, behavioral, and surveillance research in

areas of the country with SEER-quality cancer registry programs.

PROGRESS TOWARD MEETING 

THE CHALLENGE

The Plan put forth complements and extends 

recommendations of the Surveillance

Implementation Group (SIG), a review committee

created by NCI to determine what cancer surveillance research is most needed and how best to

advance our knowledge of cancer. The SIG, which

included 42 leading scientists and experts from

NCI, other Federal agencies, and the extramural

community, was asked to identify research directions and priorities and to produce an implementation plan that represented a comprehensive,

focused vision for NCI-supported surveillance

research. In 1999, the SIG produced a Cancer

Surveillance Research Implementation Plan. It

identifies five priority areas and 12 recommendations for opportunities in the study of cancer trends. 

NCI support through SEER for the

Patterns of Care and the Prostate

Cancer Outcome studies is enhancing

our knowledge about the outcomes of cancer treatment, including quality of care

and quality of life issues. In addition, the

Prostate Cancer Outcome Study, which

oversampled black and Hispanic men, will

provide us with much-needed information

on these population groups. 

The Breast Cancer Surveillance

Consortium supports eight sites throughout the

U.S. that assess accuracy, cost, and quality of

screening programs and their impact on cancer

diagnoses and survival. Recompetition for this

program will continue research support and allow

for collection of more detailed risk factor data. It

also will provide an opportunity for adding other

sites that provide screening for ethnic minority

and medically underserved populations. 

SEER investigators and NCI staff are developing a cancer survival monograph for publication in

2000. It will reflect enhanced data collection and

reporting on survival among ethnic minorities and

the medically underserved.

A new program called the Cancer Intervention

and Surveillance Modeling Network (CISNET)

is in development. Modeling is the use of mathematical and statistical techniques to integrate and

synthesize known biological, epidemiological, clin94 The Nation’s Investment in Cancer Research

For more 

information 

on surveillance

implementation

visit

http://dccps.

nci.nih.gov/

DCCPS
ical, behavioral, genetic, and economic information. Modeling techniques have been used to

describe the impact of cancer interventions (i.e.,

screening and treatment) on hypothetical cohorts

(groups), or in trial and other clinical settings.

CISNET will promote the application and extension of these models to population-based settings

to help answer “why” questions in the analysis of

cancer trends. 

Early progress is being made in working with

cancer surveillance partners to develop a National

Cancer Surveillance Program. Efforts have intensified in the past year to disseminate public use

tapes of SEER data, various software packages such

as SEER*Stat, and a broad range of Cancer

Surveillance Research Program resources through

the World Wide Web. Finally, the SEER program

is working with Oxford University Press on its

Cancer Spectrum project to make cancer statistics

more widely available through its on-line Journal

of the National Cancer Institute. 

NCI’s Challenge 95

Challenges

Resources: Studying Emerging Trends in Cancer

Collect additional data on cancer patients. $8.7 M

■ Conduct quality of care studies.

■ Conduct SEER special studies.

■ Implement Cancer Research Network project.

Connect risk factor and screening data. $12.0 M

■ Fund a Colorectal Cancer Surveillance Consortium.

■ Expand the Breast Cancer Surveillance Consortium.

■ Continue linkage studies.

Expand SEER coverage. $11.3 M

■ Add 2-5 registries.

■ Provide technical assistance for allied/pooled data registries.

■ Support special studies.

■ Provide technical assistance and quality control for infrastructure. 

■ Enhance biomedical computing capacities.

Expand methodologic studies. $6.0 M

■ Develop methods (e.g., CISNET).

■ Develop measures for risk factor assessment.

■ Improve outcomes methods and modeling.

■ Use Geographic Information Systems and mapping.

Enhance SEER as research resource. $2.3 M

■ Enhance data collection on self-reported family history of cancer.

■ Develop biospecimen resource for surveillance.

■ Expand use of rapid case ascertainment methods.

Develop new informatics initiatives. $1.5 M

Improve surveillance data dissemination. $0.8 M

Create surveillance research training opportunities. $1.0 M

Establish Centers for Population Health. $10.0 M

Management and support. $3.0 M

TOTAL $56.6 M
THE CHALLENGE

T

raining, education, and career development of

the next generation of cancer scientists is one

of our most important challenges. Scientists of the

future will need to both assimilate and create new

modalities and ways of thinking to keep up with

the rapid pace of scientific discovery and technologic advances. We will need a cadre of scientists

who can use new research models to expedite the

translation of basic scientific discoveries into

interventions and treatments for people with cancer or those at risk. Preparing the cancer research

scientists of the future is a long-term challenge

that requires us to implement new concepts and

multiple strategies, and to make targeted, sustained investments to move beyond the limitations of traditional research establishment cultures, health care financing constraints, and

socioeconomic inequities. We must sustain the

basic science that enables us to discover the

molecular reasons that normal cells become cancerous. We also must harness the potential of new

scientific disciplines such as informatics and innovative technologies for characterizing critical

genetic and cellular functions. We must train scientists who can translate these discoveries into

public benefit.

Scientists who work in different kinds of

research settings (e.g., laboratory, clinic, community) must have training across these disciplines so

they can take maximum advantage of every opportunity for translating discovery into real advances

in cancer prevention, detection, diagnosis, treatment, and quality of life. Traditional administrative divisions that separate academic areas in the

education and training of basic biological scientists, clinical scientists, public health scientists,

and behavioral scientists can be diminished by

employing more unified concepts. New ways of

educating, training, and developing scientists are

necessary to ensure that technology advances are

integrated rapidly into the cancer research enterprise and that scientists are better prepared to

work collaboratively in team settings to unravel

the complex factors contributing to human cancer. 

Moreover, we cannot afford to lose a generation

of talented new cancer researchers, or fail to

attract established scientists to the cancer research

endeavor. Delaying investment in programs that

ensure the essential training of our cancer research

workforce of the future will cause a critical gap in

the momentum of scientific discovery. 

Five crucial issues must be addressed to meet

this challenge. First, while the pool of basic scientists is of the highest quality, few are conducting

research directly related to human cancer. We

must train and encourage more basic scientists to

collaborate with clinical and population scientists.

Second, the economics of the health care system

are forcing clinical investigators away from

research into revenue-generating care. We must

develop better ways to train clinical investigators

and we must ensure that our highest quality medical scientists have protected time (i.e., time

reserved from clinical and administrative responsibilities) to conduct the research that will produce

better methods of cancer diagnosis and treatment.

Without a well trained and supported critical mass

of clinical investigators, many of the most important opportunities in patient-oriented, translational research will go untested. Third, the number of

population scientists with sufficient professional

stability who conduct early detection, epidemiology, prevention, control, risk factor, and behavioral

research is inadequate to sustain a high quality

translational research enterprise. We must develop

better ways to train population scientists in the

new interdisciplinary paradigms and increase the

number of scientists who work in these fields.

Fourth, the involvement in cancer research of scientists practicing in or from medically underserved

areas and populations, and of underrepresented

racial and ethnic minority backgrounds, is inade6 Training, Education, and Career Development

CHALLENGE

96 The Nation’s Investment in Cancer Research
NCI’s Challenge 97

Challenges

quate. We must develop new, more effective

strategies for attracting and training these individuals as scientists. Fifth, new, more powerful technologies, new disciplines, and improved bioinformatics infrastructures are likely to be critical driving forces for progress in the future. We must

develop new career paths that effectively link

these areas to the cancer research enterprise. 

THE GOALS

■ Build and sustain a critical mass of basic, clinical, population, and behavioral scientists capable of taking full advantage of the vast spectrum of future cancer research opportunities.

■ Create models for educating and training scientists to interact effectively in translating basic

knowledge into productive cancer prevention,

detection, diagnosis, and treatment strategies.

■ Attract into cancer research scientists whose

unique disciplinary orientations and/or special

technical skills can be integrated with those of

more traditionally trained scientists in biology

and medicine to generate novel, more powerful

approaches to cancer research. 

■ Increase the participation in cancer research of

underrepresented racial and ethnic minority

scientists and scientists from medically underserved areas and populations.

THE PLAN 

Objectives 

1. Provide a continuum of training and career

opportunities and protected time for research

for developing and established cancer scientists.

■ Sustain an active, vibrant National Research

Service Awards (NRSA) program to train

predoctoral and postdoctoral basic scientists

through traditional institutional and individual awards.

■ Increase participation of clinically trained individuals in basic research and clinical trials

research through special individual “mentored” awards; provide transition awards that

afford protected time for junior scientists to

develop their own research programs, and for

senior scientists to do research and mentoring.

■ Expand the number of well-trained population

and behavioral scientists in cancer research by

exploiting the NRSA program, increasing the

number of individual “mentored” awards, providing transition awards for junior scientists,

and providing senior scientists with protected

time to do research and mentor new scientists.

■ Use resources of the NCI Intramural Research

Program in collaboration with extramural

institutions to (1) enable new scientists to use

NCI’s on-campus resources to develop independent research programs (i.e., the NCI

Scholars Program) and (2) develop a critical

mass of mentors and expertise for training and

career development in areas in which few

institutions have the full range of capabilities

(e.g., prevention, radiation oncology).

■ Increase access to training and career development for basic, clinical, population, and behavioral scientists by improving the NCI Internet

information services, linking NCI opportunities

to those of other funding agencies and professional organizations, and participating more

actively at national professional meetings. 

2. Provide special training and career development

opportunities that prepare new scientists to

function in collaborative, team research settings. 

■ Prepare more basic scientists who will pursue

research relevant to human cancer and who

are able to work effectively with clinical and

population scientists. 

■ Expand institutional oncology career development programs that prepare clinically trained

individuals to become expert in clinical trials

design and implementation requiring collaboration with basic scientists. 

■ Implement new programs for population and

behavioral scientists that will prepare them to

work in collaborative, team research settings

with basic scientists and clinicians.

3. Develop partnerships with academic institutions,

industry, and other Federal and non-Federal

organizations for general and specialized training.

■ In academic institutions, enhance the role of

NCI Cancer Centers in developing and

implementing unified cancer research curricula across all of the biomedical, public health,

and social science disciplines; use education

grants to promote short-term research experiences in multiple research settings. 
■ Develop new training programs linking informatics to the biomedical sciences in collaboration with the National Library of Medicine

and the National Science Foundation.

■ Create exchange programs that encourage

NCI career award recipients to spend part of

their training experience in industry to promote academic/industrial collaborations.

■ Establish National Forums for short-term

courses in areas of emerging scientific importance (e.g., technology, genomics) that provide didactic and “hands-on” experiences to a

broad range of biomedical cancer researchers.

■ Improve communication of information

about NCI training and career development

programs to the Nation’s graduate schools,

medical schools, and schools of public health,

including minority and minority-serving

institutions.

■ Create a seamless information continuum by

electronically linking NCI information systems with those of other Federal and nonFederal funding organizations.

4. Integrate new technical and research disciplines into the cancer research enterprise.

■ Develop and implement new institutional

training instruments that can be used to integrate traditional biomedical researchers with

other non-traditional sciences (e.g., physics,

engineering, computer science) and technology developers.

■ Create the individual Diversified Sciences

Career Development Award for established scientists in non-traditional cancer research areas

who wish to switch to cancer research careers

and work in multidisciplinary research settings. 

5. Implement programs to recruit underserved

ethnic and minority individuals into cancer

research, help them begin training earlier in

their education and career, and help sustain

these individuals through each stage of career

development until a high proportion are successful independent investigators.

■ Implement the Continuing Umbrella of

Research Experiences (CURE) program that

provides a continuum of training and research

opportunities, beginning in high school and

continuing through undergraduate, graduate,

postdoctoral, and junior faculty levels.

■ Link CURE to complementary programs of

other funding agencies and professional

organizations, such as the National Science

Foundation and the American Association

for Cancer Research. 

■ Increase the participation of minority and

minority-serving institutions in cancer

research, training, education, and outreach by

supporting the establishment of long-term

partnerships with NCI Cancer Centers and

Community Clinical Oncology Programs. 

PROGRESS TOWARD MEETING 

THE CHALLENGE 

During the past year, NCI developed a strategic

plan for research training and career development. The plan is a blueprint for meeting most of

our training and career development objectives in

the basic, clinical, population, and behavioral sciences in the next decade. Progress toward meeting

this challenge has been significant but will require

concentrated attention for five years or more

before all of our critical objectives are satisfied. 

NCI has created clear career tracks offering a

continuum of opportunities that stabilize the

training and career development of basic scientists, M.D.s pursuing basic science careers, M.D.s

pursuing clinical science careers, individuals pursuing population science careers, individuals working in or from underserved areas, and individuals

from underrepresented racial and ethnic minority

groups pursuing cancer research careers. Career

tracks are strategically linked by individual “mentored” awards, bridging awards, transition awards,

established investigator awards, and institutional

program awards. NCI’s most recent progress

toward achieving its training, education, and

career development objectives include establishing

these career tracks and implementing the strategies described below.

98 The Nation’s Investment in Cancer Research
Individual Awards

■ A spectrum of Individual “Mentored” five-year

award opportunities now are in place for M.D.s

pursuing basic or clinical science career tracks

and for individuals pursuing a population science career track. 

■ Bridging Awards have been created to help

basic scientists and minorities successfully navigate the transition from a mentored scientist to

an independent junior faculty position. These

awards incorporate the concepts of “transition”

and “protected time” for basic scientists who

commit to a research career focused on human

cancer or for minority scientists pursuing a

career in any aspect of cancer research.

■ Transition Awards are three-year awards that

provide protected time for new investigators to

initiate successful research programs. They now

are in place for NCI’s two most vulnerable and

critical areas of need: medically trained doctors

in basic or clinical research, and population scientists. A transition award is being developed

for minority scientists. 

■ Established Investigator Awards allow seasoned investigators to set aside up to 50 percent

of their salary toward protected research time

and to participate in mentoring new scientists.

Those who already have independent research

support can qualify for up to five years of funding with another five years renewal through

this award. This award is in place for M.D.s in

the clinical science career track. This has been

NCI’s greatest priority as so many clinicians are

migrating from research to patient care in the

current health care delivery system. Another

established investigator award is being developed for the population sciences career track

and should be in place within a year. 

Institutional Awards

■ Institutional Program Awards are five-year

awards to institutions that select candidates for

participation in programs designed specifically

to train individuals to work in translational

research and/or team research settings. The

applications are evaluated based on the quality

of the training program and the quality of the

mentors who will participate. Of these awards,

the R25 education and career development

institutional grant is unique and specific to the

National Cancer Institute. It will be immediately important to the prevention, control, population, and behavioral sciences but can be

applied to all types of specialized interactive

training programs in the future.

■ Diversified Sciences Career Development

Awards are in the planning stages. They will be

designed to attract scientists from different disciplines to cancer research and to help build

teams of scientists who will work together to

ask and answer complex questions about cancer.

■ A spectrum of minority supplements is now

available. Combined with the Minority Career

Awards and Transition Awards, these supplements make up the new NCI Continuing

Umbrella of Research Experiences (CURE)

program. This unique NCI program will attract

young individuals from underserved areas and

populations, and underrepresented racial and

ethnic minority groups into research beginning

at the high school level and follow them proactively through each stage of their careers until

they become independent investigators.

■ Minority Institution/ NCI Cancer Center

Research, Training, Education, and Outreach

Partnerships will be initiated. The purpose of

these partnerships will be to increase and stabilize the participation of minority and minorityserving institutions in the cancer effort. The

expectation is that these partnerships will have

a major influence on the way NCI Cancer

Centers conduct outreach and education in

underserved communities and on the ways

minority institutions conduct cancer research

and train future cancer scientists.

These career tracks and training strategies, 

now being planned and implemented along with

improved Internet communications and an

increased NCI presence at national meetings, 

will ensure that all training, career development,

and education opportunities are employed fully 

by the scientific community.

NCI’s Challenge 99

Challenges
100 The Nation’s Investment in Cancer Research

Resources: Training, Education, and Career Development

Provide a continuum of training and career opportunities. $27.5 M

■ Support an array of career development awards and training programs for basic, clinical, 

population, and minority scientists, and for diversified sciences:

20 K01 (Temin Award – basic scientists working on human disease)

22 K22 (12 clinical and 10 population scientists)

20 K24 (clinical science)

10 K07 (population science)

10 K05 (population science)

24 K01 (translational research)

5 K25 (high technology)

2 K12 (institutional awards for clinical science; 10 positions each)

5 R25 (institutional awards, 3 in population science and 2 in diversified sciences, 

each with multiple positions)

118 New Awards in FY 2001

■ Create new training programs and enhance existing programs that use NCI Intramural 

Research Program resources (6 new scientists, NCI Scholars Program; 1 new intramural/

extramural training program)

Expand training and education opportunities. $11.0 M

■ Establish 2 National Forums for short-term courses in areas of emerging scientific importance.

■ Develop 2 new co-funded cancer research training models.

■ Create exchange programs that encourage NCI career award recipients (100 awardees annually) 

to spend part of their research training experience in other research settings. 

Recruit and retain more individuals from underserved populations and 

underrepresented racial and ethnic minority populations. $11.0 M

■ Provide supplements to NCI Cancer Centers for 100 minority high school and 

undergraduate students.

■ Provide supplements to Research Project Grants for an additional 12 minority scientists.

■ Provide supplements to existing training programs for minority trainees 

(8 K01, basic sciences; 3 K12 positions; 10 R25 positions). 

■ Establish 10 Minority Institution/NCI Cancer Center Research, Training, Education, 

and Outreach Partnerships. 

Improve infrastructure for developing and enhancing programs and for 

communication about NCI training and career development opportunities. $8.2 M

■ Continue developing, refining, and integrating NCI Internet-based information systems.

■ Improve communication with professional organizations about NCI training opportunities. 

■ Provide supplements to cancer centers to foster communication and outreach to scientists.

■ Improve interactions with graduate schools, medical schools, and schools of public health.

■ Recruit additional NCI staff to manage new activities.

Management and support. $3.0 M

TOTAL $60.7 M
The National Cancer Institute’s The

Nation’s Investment in Cancer Research

is a truly collaborative effort. As in the

past, the document has benefited from

the insights, perspectives, contributions,

commitment, and review of countless

people both within NCI and in research

and academic institutions and professional organizations throughout the country.

Two NCI offices, the Office of Science

Policy and the Office of Budget and

Financial Management, played key roles 

in developing and assembling information

for this book. In particular, several members of NCI staff merit special recognition

for their contributions. Cherie Nichols provided leadership, motivation, insight, and

counsel. Her efforts sparked, guided and

sustained the project’s progress from initial plan to final printing. Catherine Law,

Anna Levy, Jane Lockmuller, Kate Nagy,

and Anne Tatem conceptualized, wrote,

and edited the vast majority of the text.

Their exceptional skills and perseverance

were essential in the production this document. We are grateful to Susan Rossi for

her scientific input and editing, to Cheryl

Parrott for her writing contributions and

editing skills, and to Susan Waldrop for

her writing contributions. We are also

indebted to Suzanne Reuben for her excellent editing and writing contributions.

Finally, we are grateful to John Hartinger

and the staff of the Office of Budget and

Financial Management for their fiscal

knowledge and guidance.

Extraordinary Opportunity and

Challenge Champions

This year each Extraordinary Opportunity

and Challenge was represented by “champions” - members of NCI staff expert in

these areas of special research investment

who aided in crafting the vision, plans,

progress, and resources for each opportunity or challenge. The efforts of these

champions and countless NCI staff members who assisted them helped us to

articulate this critical information. 

Extraordinary Opportunities

Genes and the Environment - Dr. Richard 

Klausner, Dr. Joseph Fraumeni

Cancer Imaging - Dr. Robert Wittes, 

Dr. Ellen Feigal

Defining the Signatures of Cancer Cells: 

Detection and Diagnosis - Dr. Richard 

Klausner, Dr. Peter Greenwald

Molecular Targets of Prevention and 

Treatment - Dr. Richard Klausner, 

Dr. Robert Wittes

Research on Tobacco and Tobacco-Related

Cancers - Dr. Richard Klausner, 

Dr. Barbara Rimer

Cancer Communications - Dr. Richard 

Klausner, Dr. Barbara Rimer

Challenges

Investigator-Initiated Research - 

Dr. Marvin Kalt, Dr. Norka Ruiz Bravo

Centers, Networks, and Consortia - 

Dr. Ellen Feigal, Dr. Brian Kimes

National Clinical Trials Program - 

Dr. Robert Wittes, Dr. Michaele 

Christian

Informatics and Information Flow - 

Mr. James Silva, Ms. MaryAnn Guerra

Studying Emerging Trends in Cancer - 

Dr. Robert Hiatt, Dr. Brenda Edwards

Training, Education, and Career 

Development - Dr. Brian Kimes

FY 2001 Editorial Board

The Nation’s Investment in Cancer

Research serves two important functions:

it describes NCI’s research portfolio and

the future path we have identified as the

most direct route to conquering cancer.

With this in mind, we enlisted the help of

several NCI staff with expert scientific

knowledge, an over-arching perspective

on the Institute’s activities and goals,

and keen understanding of promising

opportunities in cancer research. These

individuals, our Editorial Board, helped

shape the content of this book.

Dr. Norka Ruiz Bravo, Ms. Julianne

Chappell, Dr. Ellen Feigal, Mr. John

Hartinger, Dr. Barry Kramer, Dr. Alfred

Knudson, Dr. Edison Liu, Dr. Barbara

Rimer, Dr. Margaret Tucker, Mr. Paul 

Van Nevel.

FY 2001 Bypass Planning Committee

We thank the members of our planning

committee who helped to ensure that this

document clearly and accurately describes

the excitement and promise of our

research efforts, NCI’s needs and plans,

and the vision for the future of our

research programs.

Dr. Richard Klausner

Director

Dr. Alan Rabson

Deputy Director

Dr. Robert Wittes

Deputy Director, Extramural Science and

Director, Division of Cancer Treatment 

and Diagnosis

Dr. Norka Ruiz Bravo*

Deputy Director, Division of Extramural

Activities, National Institute of General

Medical Sciences

Dr. Ellen Feigal

Deputy Director, Division of Cancer

Treatment and Diagnosis

Dr. Joseph Fraumeni

Director, Division of Cancer Epidemiology

and Genetics

Dr. Paulette Gray

Deputy Director, Division of Extramural

Activities

Dr. Peter Greenwald

Director, Division of Cancer Prevention

Ms. MaryAnn Guerra

Deputy Director, Management

Dr. Joseph Harford

Associate Director, Special Projects

Mr. John Hartinger

Associate Director, Financial Management

Dr. Marvin Kalt

Director, Division of Extramural Activities

Dr. Alfred Knudson

Special Advisor, Division of Cancer

Epidemiology and Genetics

Dr. Edison Liu

Director, Division of Clinical Sciences

Ms. Cherie Nichols

Assistant Director, Science Planning and

Assessment

Dr. Barbara Rimer

Director, Division of Cancer Control and

Population Sciences

Dr. Susan Sieber 

Associate Director, Special Projects

Dr. George Vande Woude

Director, Division of Basic Sciences

Ms. Susan Waldrop

Assistant Director, Program Coordination

Dr. Sherry Mills, Chair

Extramural Advisory Board

Dr. Allan Weissman, Chair

Dr. Margaret Tucker

Intramural Advisory Board

Dr. David Livingston, Chair

Board of Scientific Advisors

Dr. Martin Abeloff, Co-chair

Dr. Bruce Stillman, Co-chair

Dr. Matthew Scharff, Member

Board of Scientific Counselors

Ms. Lillouise Rogers, Member

Director’s Consumer Liaison Group

Dr. J. Michael Bishop, Chair

Dr. Philip Schein, Member

Dr. Phillip Sharp, Member

Ms. Ellen Stovall, Member

National Cancer Advisory Board

* Former Acting Director, Division of 

Cancer Biology, NCI

Acknowledgments
NIH Publication No. 99-4373 T206

October 1999 

Additional copies of The Nation’s Investment in Cancer Research: A Budget Proposal for Fiscal Year 2001

can be ordered by fax at 301-330-7968, by e-mail at cisocc@nih.gov, or by phone at 1-800-4-CANCER. 

Or, you may view the document and previous Bypass Budgets online at http://www.nci.nih.gov

FOR ADDITIONAL INFORMATION ON:

■ CANCER visit us online at http://cancernet.nci.nih.gov where patients, health professionals, and the public

can find information about the different types of cancer, screening, diagnosis, and state-of-the-art care. 

Or, call NCI’s Cancer Information Service at 1-800-4-CANCER to speak with an information specialist.

■ CLINICAL TRIALS visit the Physician Data Query (PDQ) data base at http://cancernet.nci.nih.gov or visit our 

clinical trials resource, cancerTrials, at http://cancertrials.nci.nih.gov, which provides information about

ongoing prevention, detection, diagnosis, and treatment clinical trials – including links to data bases of 

ongoing studies and general information about clinical trials. 

■ CANCER CENTERS call NCI’s Cancer Centers Branch at 301-496-8531 or visit 

http://www.nci.nih.gov/cancercenters/. For a list of NCI-designated Cancer Centers visit

http://www.nci.nih.gov/cancercenters/centerslist.html

■ GRANTS AND CONTRACTS visit NIH’s Grants and Contracts page at http://www.nih.gov/grants

■ TRAINING, EDUCATION, AND CAREER DEVELOPMENT call NCI’s Cancer Training Branch at 301-496-8580. 

A new Web site is being developed and will be accessible from NCI’s home page at http://www.nci.nih.gov

■ SURVEILLANCE visit the Surveillance, Epidemiology, and End Results (SEER) Program at

http://www.seer.ims.nci.nih.gov