National Cancer Institute

The Nation’s Investment in Cancer Research

Connecting the Nation’s

Cancer Community

AN ANNUAL PLAN AND BUDGET PROPOSAL FISCAL YEAR 2010

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health
The NaTioNal CaNCer iNsTiTuTe 1

Director’s Message

i

n the nearly four decades since passage of the landmark 

National Cancer act of 1971, america’s progress against 

cancer has been significant and steady – although, typical of 

science, most often measured in small increments. in 1991, cancer death rates began to drop, by about one percent each year. 

of late, many cancer incidence rates have also been decreasing 

on an annual basis.

This incremental progress is particularly impressive, when viewed 

through the prism of other, more sobering statistics. Cancer, as 

a disease burden, is rising across the globe. By the year 2010, 

cancer is expected to pass heart disease as the number-one killer. 

Clearly, our work – in the united states and worldwide – is far 

from complete.

Cancer affects each of us, whether directly, as a patient, or in 

the reflected struggles of a loved one or a friend. it is no surprise 

that, as director of the National Cancer institute, the questions 

i most often hear – from cancer survivors, from patient advocates, and from legislators – begin with “What will it take...” 

What will it take, i am asked, to accelerate the downward curve 

of cancer death rates? What will it take to deliver on the promise that cancer can be made more chronic than killer? What will 

it take, in dollars, to rid us of this burden?

This document is an attempt to bring some realistic answers, 

with appropriate dimensions, to these questions. it is based on 
science – on the exciting forefronts in laboratory research that 

are vastly expanding our knowledge of cancer’s origins, processes, and weaknesses. it is based on the need to more rapidly 

translate this new knowledge into safe, effective, targeted interventions for cancer patients. it is about the resources that could 

hasten our efforts. it is about the importance of increasing our 

intellectual capacity, our workforce, to take full advantage of 

the opportunity to make real changes.

in sum, this document is the National Cancer institute’s professional judgment of what a financial infusion could make possible and how NCi would spend those monies.

in the pages ahead, i hope you will also recognize NCi’s deep 

commitment to outstanding science that benefits all americans. 

Cancer is – and will continue to be – a model for the study of 

disease biology, for new thinking about the delivery of healthcare, for the development of electronic medical records, and for 

a healthcare system based on the uniqueness of each individual. 

Those responsibilities, those commitments, drive us – in NCi’s 

own laboratories, through the thousands of outstanding scientists we support across america’s cancer research enterprise, and 

in the vital collaborations we foster around the world. This document is, after all, about progress, about opportunity, and about 

reducing the cancer burden for all people in every nation.

John e. Niederhuber, M.D.

Director, National Cancer Institute
The NaTioNal CaNCer iNsTiTuTe T N N C TTi N T 3

Following Important Leads

Less than a decade into the new century, America’s cancer research enterprise – led and 

facilitated by the National Cancer Institute – is coming to deeply understand cancer’s causes, 

inner workings and complexities at an ever accelerating pace. Spurred by the 2003 completion 

of the landmark Human Genome Project, we now understand, as never before, that cancer is 

primarily a disease of our genes – both in the germline DNA passed on to us by our parents and 

in the changes to our genes that accumulate over a lifetime. The tumor, as we have known for 

some years now, is not a single entity. Scientists have learned that cancers are collections 

of aberrant cells, which may rely on seemingly normal tissue in the microenvironment that 

surrounds the tumor, in order to communicate, grow, and metastasize. As we continue to make 

many unexpected discoveries about cancer’s common pathways and stunning intricacies, each 

discovery may also reveal an opportunity for solutions to a complex problem. The pages that 

follow highlight some of the exciting cancer research opportunities before us today – and 

some of the visionary scientists who have greatly enhanced our knowledge of cancer.
4 T h e N aT i o N a l C a N C e r i N s T i T u T e

Tumor Microenvironment 

Much of the basic cancer research conducted over the past 30 years has been 

focused on the cancer cell, without particular concern for its surroundings. researchers are finding, however, that tumor 

cells do not live independently. To survive 

and proliferate, tumors require assistance 

from the microenvironment of cells, molecules, and blood vessels immediately surrounding them.

“Non-cancerous cells recruited from the 

host are now seen as rate-limiting determinants of how well the tumor grows and 

how it is able to metastasize and establish 

itself in distant organ sites,” explained 

robert a. Weinberg, Ph.D., a member of 

the Whitehead institute for Biomedical 

research at the Massachusetts institute 

of Technology. Dr. Weinberg discovered 

the first human oncogene, which directs 

tumor growth, as well as the first tumor 

suppressor gene.

at the heart of the tumor microenvironment is the signaling that goes on between 

cells. research in this area is yielding evidence of a greater number of cytokines, 

which are proteins that guide interactions 

between cells. These cytokines facilitate 

talk between pre-cancerous cells and other 

cells that have been recruited to build a 

tumor’s framework. The basic characteristics of malignant cancers are developed 

and stimulated by signals originating in 

this framework. 

Because standard research models and 

methods for analyzing cancer cell behavior cannot adequately capture the complex nature of the tumor microenvironment, more advanced models are now 

being developed, in order to realistically 

mimic the signaling pathways and interaction between the tumor and its surrounding environment. a highly sophisticated 

computer model, developed in conjunction with scientists from disciplines such 

as mathematics and bioinformatics, is 

providing a fuller picture of cancer as a 

biological system.

one eventual use for these so-called in 

silico models could be to generate a virtual 

model of individual patients’ tumors, then 

simulate how various treatments would affect the tumor and patient, pointing to the 

most effective and least toxic therapy. such 

computer models hold great potential for 

studying diseases other than cancer.

“Non-cancerous cells recruited from the host are now seen as ratelimiting determinants of how well the tumor grows and how it is 

able to metastasize and establish itself in distant organ sites.” 

 — robert A. WeINberg, ph.d.
The NaTioNal CaNCer iNsTiTuTe 5

Because of the fundamental importance 

of this area of research, NCi launched a 

tumor microenvironment initiative in 

2006 with the funding of 10 programs, 

most of which are university based, and 

the establishment of a network to facilitate 

the programs. The primary objective of 

the initiative is to delineate mechanisms of 

tumor-host interactions in cancer by better 

understanding the role that the stroma, or 

supporting tissue and elements surrounding the tumor, plays in initiation, progression and metastases of a tumor. 

Tumor Stem Cells

in the mid-1990s, Canadian researchers 

discovered the first cancer-initiating cells 

in patients with acute myeloid leukemia. 

These so-called cancer stem cells, which 

make up less than five percent of a tumor, 

may, in fact, be the cells that are the earliest 

precursors of cancer’s spread and the cells 

most resistant to conventional treatments.

in the years since that initial discovery, 

cancer stem cells have been identified in 

other blood-borne cancers, along with 

brain, breast, ovarian, and, most recently, 

colon cancers. By any measure, the science of cancer stem cells is both a young 

avenue of investigation and an extremely 

promising one. scientists believe that some 

tumors contain small populations of these 

self-renewing cells. They also note that the 

tumor microenvironment is crucial to a 

complete understanding of stem cells, as 

the microenvironment’s noncancerous host 

tissue plays a major role in cancer progression, in the nourishment of the tumor, and 

in its ability to communicate.

NCi supports research to isolate cancer stem cells, based on markers that are 

shared by normal tissue stem cells of the 

same type – and occasionally by other 

cells, as well. The hope is that scientists 

can develop therapies that target and control cancer stem cells before they lead to 

metastasis – or, via some fascinating new 

insights, engineer certain other tissue stem 

cells to create healthy organs.

among the many investigators NCi supports across the united states is anthony 

atala, M.D., from Wake Forest university, 

a leader in the emerging field of tissue engineering using stem cells. recently, Dr. atala isolated stem cells through a procedure 

familiar to millions of expectant mothers: 

amniocentesis. This common technique, 

normally performed about 16 weeks into 

pregnancy, tests the fluid that surrounds 

a growing fetus for signs of genetic disorders. as Dr. atala has noted, amniotic 

fluid cells are also proving useful for other 

areas of scientific study and may, in time, 

be therapeutically valuable, since they will 

not form tumor cells, as embryo-derived 

cells can. Furthermore, because they grow 

slowly, amniotic fluid cells can also be 

more readily controlled.

it is important to remember that cancer stem 

cells have only recently been discovered. as a 

cautionary example, a recent scientific publication suggests that many more tumor cells 

have tumor initiating potential than previously thought. To answer fundamental questions about cancer stem cells, scientists will 

need to develop more efficient techniques for 

isolating the cells and maintaining them in 

culture, as Dr. atala has done. single-cell 

analyses will also likely be needed to distinguish events present in cancer stem cells 

from the more differentiated cells that make 

up the majority of the tumor.
6 T h e N a T i o N a l C a N C e r i N s T i T u T eTi N NT N C

Anthony Atala on Tissue Regeneration and Stem Cells

Using a process he likens to “baking a layer cake,” dr. Atala is creating new organs 

and other tissues in the laboratory. dr. Atala, director of the Wake Forest University 

Institute for regenerative Medicine, leads a team of more than 150 investigators 

doing this transformative work. the researchers remove postage stamp-size tissue samples 

from cancer patients. “We start by placing cells, one layer at a time, into three dimensional 

scaffolding, and then we place this new tissue into the body for baking,” said dr. Atala. In a 

recent clinical trial at thomas Jefferson University hospital in philadelphia, a patient had 

a bladder transplant – with a new organ grown from her own cells. Just eight weeks after 

physicians harvested the patient’s tissue, her new bladder was in the operating room ready 

for transplant. this technique shows promise to move forward from the experimental stage. 

private industry bought the license and is now producing the bladders that dr. Atala and his 

group created at Wake Forest. 

the biggest challenge, dr. Atala says, is to get cells to grow in large quantities outside the 

body, and that is where stem cells may play a vital role. peering into the future, dr. Atala 

says he would like to induce regeneration inside the body, by using stem cells to regenerate 

part of an organ at the site of injury or disease. Ultimately, “studying cancer stem cells will 

open the window to understanding how to best use a patient’s own cells for cancer therapy, 

because you want to make sure the cells you’re producing are normal cells. From this better 

understanding we should also be able to figure out what is the switch that could make them 

abnormal.”

Advances in regenerative medicine have been made possible by gathering and pooling 

expertise in bioengineering, cell biology, physiology, surgery, molecular biology, and other 

fields. “NCI plays a major role in the acceleration of these new technologies,” dr. Atala 

noted. “this technology has broad-reaching implications for all types of diseases, not just 

for cancer.” 
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 7

Signal Transduction Pathways

signal transduction pathways are communication routes for transmitting information between cells and within cells. simply 

put, these pathways are like electrical circuits made from molecules, which deliver 

signals that drive decisions about whether 

cells will proliferate or die; whether they 

will invade surrounding normal tissue; 

whether new blood vessels will grow into 

the tumor to bring essential oxygen and 

nutrients; and whether cells will travel to 

other sites in the body. NCi is exploring 

two areas of interest in this field: cross 

talk and termination of signaling. 

Cross talk, in which a signal jumps from 

one pathway to another, permits more finely 

tuned regulation of cell activity than do individual, independent pathways. however, 

inappropriate cross talk can cause messages 

to be misinterpreted or not delivered.

after a signaling process has been initiated and the information has been transduced, or transferred, to affect cellular processes, the specific signaling processes must 

be terminated. Without such termination, 

cells lose their responsiveness to new signals.

signaling processes that fail to properly terminate can lead to uncontrolled cell growth 

and the possibility of cancer. 

in order to better understand the importance 

of controlling and regulating complex signaling pathways, NCi’s cancer Biomedical 

informatics Grid program, better known as 

caBiG , is developing a tool called Biologi ® -

cal Pathway exchange as a data standard 

for the modeling of biological pathways. 

This tool should be of great value to scientists in the field of proteomics, where signaling pathways are key to understanding how 

proteins talk to each other.

NCI

athwayp

rSignal t ansduction 

RNA Interference

our understanding of the role that rNa 

plays in cellular processes and in cancer 

has evolved rapidly this century. Messenger, transfer, and ribosomal rNa are still 

vitally important to the cell as a translation 

mechanism, but regulatory rNas are now 

known to play a very important role as well. 

MicrorNa can block translation or accelerate cellular degradation and small interfering rNas (sirNa) can act in a similar 

manner. and there are a number of other 

types of rNa that can play an important 

role in activating or blocking important 

cancer pathways.
8 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

The regulation of gene expression by 

microrNas and sirNas is called rNa 

interference, or rNai, for short. This 

phenomenon has recently been exploited 

to develop molecular tools for cancer research. By injecting short strands of rNa 

molecules into cells, scientists are now 

able to silence, or turn off, certain genes. 

This technique allows experiments, which 

used to take months or years, to be completed in weeks or even days. 

use of rNai has also been enabled by 

new generations of highly-efficient, costeffective, high-throughput genetic screening techniques that make it possible to 

identify genes associated with cancer. isolating genes that control disease progression will lead to identification of potential 

targets and, in turn, to new targeted cancer 

therapeutics. 

“high-throughput sequencing will change 

everything. it will tell us about the cell 

state in the tissue, and not in just cell lines,” 

said Nobel laureate Phillip a. sharp, 

Ph.D., of the David a. Koch institute for 

integrative Cancer research at MiT. 

“We are going to accelerate the rate at 

which we’re going to be able to effectively treat cancers, and i think we will 

find ourselves in a 10 to 15 year window 

where we will see that many of the cancers that develop in mid-aged and young 

people will be treatable for very long periods of time.”

rNai can also be used to investigate the 

mechanism of action of drugs that are, for 

reasons unknown, effective against cancer. 

in addition, rNai screening can be used 

to identify genes that enhance the ability 

of chemotherapy to fight cancer. 

“We need to look, at a basic level, at particular cells and particular states, as that’s 

the only way to design drugs and interventions,” continued Dr. sharp. “This wasn’t 

possible in the pre-genome era – we didn’t 

have enough granularity and now we do, so 

we’ve got a specific way of intervening.”

one particular area of study, the regulation of gene activity by methylation, could 

benefit from advances in rNai techniques. 

Methylation involves the addition of 
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 9

methyl groups (molecules made up of one 

carbon atom with three hydrogen atoms 

attached) to DNa or proteins. stephen 

Baylin, M.D., and his team at Johns hopkins university are very involved in the 

field of epigenetics, which centers around 

methylation, and they are looking at how 

gene expression may be caused by mechanisms other than changes in the underlying DNa sequence. The researchers used 

high-throughput screening techniques to 

study a large pool of genes thought to be 

involved in cancer. Their aim was to identify genes with potential prognostic value. 

They found that 36 of 189 genes they 

had previously identified as being associated with breast or colon tumor development were often hypermethylated. rNai 

techniques may allow them to confirm or 

refine their findings.

raisiNG The suCCess raTe For researCh ProJeCT GraNTs aND raisiNG The averaGe aWarD 

Per GraNT WoulD require $340 MillioN.

eNhaNCiNG BioMeDiCal CoMPuTiNG CaPaBiliTies To CaPiTalize oN virTual MoDels Will 

require aN aDDiTioNal $45 MillioN.

Genome-Wide Association Studies

one of NCi’s promising avenues of research, 

genome-wide association studies (GWas), 

has begun to reveal some of the key genetic 

factors that affect risk for many cancers. 

Genome-wide association studies involve 

two groups: those with a given cancer and 

a group of equal size that does not have 

the disease. Through genetic characterization, followed by finer and finer mapping 

and analysis, scientists are able to identify 

common genetic aspects for the cancers being studied. These new findings, in breast, 

prostate, colon, and other cancers, have 

raised hopes that genetic profiles based on 

germline genetic variation could identify 

individuals at high risk for cancer and also 

identify who might benefit from a variety 

of interventions.

across all diseases, in just the last three 

years, genome-wide association studies 

have identified more than 150 common 

markers associated with over 40 common 

diseases. Yet, as stephen J. Chanock, M.D., 

chief of NCi’s laboratory of Translational 

Genomics in the Division of Cancer epi-

“high-throughput sequencing will change everything. It will tell us 

about the cell state in the tissue, and not in just cell lines.”

— phILLIp A. ShArp, ph.d.
10 T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T

demiology and Genetics, often reminds 

colleagues, we are “at the beginning of the 

beginning.” Genome-wide association studies will be the basis for future laboratory 

studies, with the goals of regulating gene 

expression and understanding cell biology, 

in order to fully comprehend alterations in 

cellular function and to design novel gene 

and drug therapies that will be effective 

at the earliest possible points in cancer’s 

development. 

importantly, the vast expansion of genome-wide association studies in u.s. 

and international laboratories has benefitted from a tremendous boost in technology. The human Genome Project cost 

approximately $2.7 billion to complete. 

according to Science, by 2006, a draft genome sequence of the rhesus monkey cost 

$22 million. Today the race is on for the 

$1,000 genome sequence that can be completed in virtually real time. so, in addition to the boon in technology, the costs 

saved by advancing technology may be as 

tremendous.

iNvesTiNG iN GWas aND oTher iNiTiaTives 

ThaT MaKe uP NCi’s iNTraMural researCh 

ProGraM WoulD require $100 MillioN. 

We are “at the beginning of the beginning.”

— StepheN J. ChANoCk, M.d.
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 11

The Cancer Genome Atlas

in addition to Genome Wide-association 

studies, which seek to identify common 

DNa variants associated with cancer, NCi 

is conducting crucial studies into the entire genetic composition of many cancers. 

The Cancer Genome atlas (TCGa) project, begun in 2005 as a collaboration between NCi and the National human Genome research institute (also part of the 

National institutes of health), has utilized 

and helped develop tools and technologies 

to generate impressive amounts of data on 

the genetic make-up of tumors. in september 2008, TCGa reported the first results 

of its large-scale, comprehensive study of 

glioblastoma, the most deadly form of 

brain cancer. The study, reported in Nature, identified three previously unrecognized mutations that occur with significant frequency, and the delineation of core 

pathways disrupted in this type of brain 

cancer. one of the most exciting results 

is an unexpected observation that points 

to a potential mechanism of resistance to 

a common chemotherapy drug used for 

brain cancer.

at present, TCGa, through its network of 

characterization, sequencing, and analysis 

centers, is also working on lung and ovarian cancers. Moving forward, TCGa has 

established a goal of rigorously, comprehensively, and reproducibly characterizing 

the genomes of four to six tumor types per 

year – with all results both ensuring patient privacy and providing ready access 

to the research community.

exPaNDiNG TCGa WoulD require aN 

aDDiTioNal $200 MillioN.

Infectious Etiology

some cancer-associated viruses appear, in 

rare cases, to cause cancer. other viruses, 

however, substantially increase the risk for 

cancer and the burden of this disease in the 

population. For example, hiv-1 infection 

is responsible for substantial increases in 

some cancers in young adults in the united 

states. although it is not yet clear how to 

prevent most cancers that occur among 

hiv-infected people, understanding the 

transmission routes of the virus and finding 

preventive measures could lower the incidence of infection, and the subsequent risk 

of non-hodgkin’s lymphoma and Kaposi’s 

sarcoma. Previously, only a small percentage of cancers were thought to be caused 

by infectious agents, but current analyses 

put that number closer to 18 percent. 

similarly, reducing the transmission of human T-lymphotropic viruses will lower the 

incidence of adult T-cell leukemia/lymphoma. Furthermore, knowing which cancers 

are associated with different viruses helps 

to promote targeted cancer screening, early 

detection, treatment, and prevention. 

scientists in the NCi’s infections and immunoepidemiology Branch are using principles of both infectious and chronic 

disease epidemiology to investigate the 

biology and transmission of cancer-causing 

organisms and to clarify the relationship 

between infectious organisms and cancer 

and other diseases. in addition to studying viruses that are associated with cancer, 

these scientists are also investigating other 

microorganisms, such as Chlamydia pneumoniae, which have been linked to lung 

cancer, and sexually-transmitted viruses that 

may cause prostate cancer. 
12 T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T

NCi’s Center for Cancer research supports researchers who are making important advances in understanding the 

relationship between infection and cancer. 

These scientists are investigating tumorcausing viruses and bacteria at the molecular level. areas of investigation include 

genes and gene products that regulate cell 

growth and pathways that contribute to 

the development of cancer. 

The knowledge gained in studying the 

links between viruses and certain types 

of cancer has been instrumental in helping scientists develop strategies to fight 

cancer, such as vaccines directed against 

human papillomaviruses to prevent cervical cancer and hepatitis B virus, which has 

been associated with some forms of liver 

cancer. The study of viruses has also been 

an important tool in revealing the mechanisms that are involved in carcinogenesis. 

thin-section 

transmission electron 

micrograph depicts 

the ultrastructural 

details of a number of 

 hIV virus particles.

photo courtesy CdC.
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 13

Cancer Vaccines and Immunotherapy

Many deadly infectious diseases that were 

capable of killing millions of people have 

been tamed because of vaccines, which stimulate the immune system to recognize and 

attack pathogens before they cause disease. 

in the future, this approach may also be 

effective in preventing and fighting cancer. 

a major step toward this goal came when 

the FDa approved a vaccine for the prevention of human papillomavirus (hPv) 

infection. NCi investigators throughout 

the institute were involved in the discovery that hPv is a major cause of cervical cancer. among these were Douglas 

lowy, M.D., and John schiller, Ph.D., 

of the Center for Cancer research, who 

were instrumental in the discovery of the 

virus-like particle technology that led to 

the vaccine’s development. 

hPv vaccines represent one type of cancer 

vaccine, which may prevent cancer before 

it occurs, while others, termed therapeutic 

cancer vaccines, may help turn a patient’s 

immune system against already-existing 

cancer cells. 

using a mouse model, Jay Berzofsky, 

M.D., Ph.D., of the Center for Cancer 

research’s vaccine Branch, developed a 

vaccine containing proteins from breast 

cancer cells that is capable of inducing 

immune responses strong enough to kill 

large breast cancer tumors and tumors 

that have metastasized to the lungs. These 

results show the potential for a vaccine 

that can stimulate the production of antibodies directed against a cell surface receptor such as her2, which is found on 

breast cancer tumors. 

vaccines may be most effective as adjuvant therapy following surgery to remove 

the bulk of the cancer. They can be administered in conjunction with other standard 

treatments, such as chemotherapy or radiation, and given with cytokines to enhance the immune response. 

More than a dozen vaccines are in or nearing 

phase iii trials to refine their use, including dosing, booster schedules, and the site 

of vaccine administration. But for now, 

the FDa has not approved any therapeutic cancer vaccines. 

“the beauty of using the immune system to fight cancer is its 

exquisite specificity. radiation kills everything in its path. 

Chemotherapy kills many cells besides cancer cells.”

— JAy berzoFSky, M.d., ph.d. 
14 T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T

in another example, steven a. rosenberg, 

M.D., Ph.D., NCi’s chief of surgery, has 

been successfully using altered versions of 

a patient’s own white blood cells to recognize and attack the cells of advanced melanoma. The ability to genetically engineer 

human white blood cells to fight against 

cancer, called adoptive Cell Therapy, has 

opened possibilities for many other types 

of cancer. Dr. rosenberg and his colleagues 

are currently researching use of adoptive 

Cell Therapy in metastatic melanoma and 

renal cell cancer, among others. 

“The beauty of using the immune system 

to fight cancer is its exquisite specificity,” 

says Dr. Berzofsky. “radiation kills everything in its path. Chemotherapy kills 

many cells besides cancer cells. The immune system – if you could take full advantage of it – can be so specific that it 

can kill one cell and not all the other cells 

around it. You could potentially eliminate 

cancer cells without having the side effects 

of other therapies.”

“We have been able to generate a very large number of immune cells 

that appear in the blood and constitute a majority of the immune 

system of the patient.”

— SteVeN A. roSeNberg, M.d., ph.d.

HIV/AIDS 

When the first signs of the aiDs epidemic 

appeared, NCi scientists were at the forefront of the effort to identify hiv as the 

cause of aiDs, characterize how it hijacked cellular machinery, and, in turn, 

develop the first treatments for it. They 

were able to quickly apply their expertise 

in epidemiology, cancer, retroviruses, cell 

biology, the immune system, and drug development to this public health crisis.

a research team, led by robert Gallo, 

M.D., then at NCi’s laboratory of Tumor 

Cell Biology, discovered the first two human retroviruses, hTlv-1 and -2, which 

laid the groundwork for the co-discovery 

of hiv. This team also led the development of the first diagnostic blood test for 

hiv infection. soon thereafter, other NCi 

researchers, including robert Yarchoan, 

M.D., of NCi’s hiv and aiDs Malignancy 

Branch, began to seek effective therapy for 

aiDs, and discovered or co-developed the 

first effective drugs – azT (zidovudine), ddC 
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 15

(zalcitabine), and ddi (didanosine). in particular, this group identified the anti-hiv 

activity of these drugs and, with support 

from other NCi components, conducted 

initial clinical trials with these agents. 

NCi’s Center for Cancer research currently 

has one of the largest and most productive hiv/aiDs research programs in the 

world. researchers in the Center for Cancer research’s hiv and aiDs Malignancy 

Branch, the hiv DrP (Drug resistance 

Program) host virus interaction Branch, 

and vaccine Branch are continuing to 

make advances in hiv/aiDs research. all 

of this work lays an important foundation 

for current research into the viral aspects 

of cancer development.

among these advances are the identification of genetic mutations that appear to 

protect against hiv infection or slow its 

progression, new insights into hiv viral 

diversity that contributes to drug resistance, and the development of new treatments for aiDs-related cancers, including 

Kaposi’s sarcoma and lymphoma. NCi 

researchers also are at the forefront of efforts to develop both preventive and therapeutic hiv vaccines and new treatments 

derived from natural products.

Computer graphic of 

tgf-beta, a cytokine that 

regulates many cellular 

functions including 

cell proliferation, 

differentiation, adhesion 

and migration. 

NCI, dr. Michael Sporn

Antibodies and Cancer

antibodies are proteins produced by the 

body’s immune system that are directed 

against antigens, which are usually associated with molecular components of foreign and infectious agents, such as viruses 

and bacteria. researchers can use laboratory-created antibodies, called monoclonal antibodies, in a similar manner to 

detect antigens in biological samples that 

may play a role in the development of cancer and thus may be good targets for new 

cancer therapies. Well-characterized antibodies may speed the identification of key 

proteins and peptides. 

one of the most significant roadblocks of 

advanced molecular diagnostic techniques 

like proteomics is a lack of high-quality 
16 T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T

and well-characterized reagents. This barrier was recognized by the NCi, which 

led to the development of the antibody 

Characterization laboratory. The antibody 

Characterization laboratory at NCi’s 

laboratories in Frederick, Md., part of 

the Clinical Proteomic Technologies for 

Cancer initiative, performs sophisticated 

testing to analyze and validate antibodies 

– highly critical tools used in research and 

diagnostic laboratories around the world. 

“as industry and academia invest significant resources in the promise of proteomics and ultimately molecular-based 

tools, well-characterized antibodies will 

be vital to advancing these disciplines,” 

said henry rodriguez, Ph.D., who directs 

NCi’s Clinical Proteomic Technologies for 

Cancer initiative. “This is especially true 

of proteomics, where an antibody can be 

used to recognize a unique protein in the 

midst of millions of other proteins that the 

human proteome comprises.” 

eNhaNCiNG TeChNoloGY DeveloPMeNT 

iN CliNiCal ProTeoMiCs WoulD require 

$35 MillioN.

Nanotechnology

Nanotechnology materials are so small – 

less than one-billionth of a meter in size 

– that they are measured on a molecular 

scale. Many are so tiny that they can penetrate a tumor cell, and are already being 

used in imaging to make a tumor light 

up during an Mri scan. others are being employed to convert magnetic fields 

into heat, thus destroying cancer cells. in 

the near future, nanoscale devices will be 

available to detect the presence of cancer 

at its earliest stages and to deliver targeted 

anticancer agents to the tumor. 

one of today’s challenges is characterizing these materials. For example, slight 

changes in size or surface chemistry can 

dramatically influence a physiological response and make a significant difference 

in safety or potency. laboratory methods 

used to evaluate physicochemical or immunological properties, and assays routinely used in preclinical characterization 

of conventional pharmaceuticals, often 

yield spurious results when applied to 

nanoparticle samples. 

NCi’s Nanotechnology Characterization 

laboratory (NCl) is an important component of the larger alliance for Nanotechnology in Cancer. NCi, in partnership 

with the National institute of standards 

and Technology and the FDa, is analyzing 

the growing number of nanotechnology 

products that have potential in the detection, diagnosis, and treatment of cancer. 

The NCl’s primary focus is to help move 

these products towards clinical trials.
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 17

The NCl performs physiochemical characterization and safety and toxicity characterization, including both laboratory 

tests and animal studies, and provides information needed to help investigators. To 

date, the NCl has characterized over 130 

different nanomaterial samples including liposomes, gold colloids, quantum dots, and 

metal oxides – submitted from laboratories 

in academia, industry, and government. 

“at the NCl, we are evaluating nanoparticles and devices to inform the regulatory process and support environmental, 

health, and safety research of nanotechnologies,” said scott McNeil, Ph.D., 

director of the NCl. 

eNhaNCiNG TeChNoloGiCal eFForTs 

arouND NaNoParTiCles aND ProTeiNs 

WoulD require $40 MillioN.

“green brushes”

researchers at the 

“emory/ georgia tech 

Center of Cancer 

Nanotechnology 

excellence are 

creating novel arrays 

of nanowires that 

are being used to 

sense cancer 

biomarkers, 

manipulate cancer 

cells, and convert 

mechanical energy 

into electricity 

to power other 

nanodevices.

Image courtesy of 

professor z.L. Wang, phd, 

georgia Institute of technology.

Systems Biology 

The growing field of systems biology incorporates a broad view of bioinformatics 

and how data applications and complex 

mathematics apply to cancer. Current 

NCi-supported research in model organisms, computational biology, and signaling, just to name a few, are all moving forward at a faster pace, thanks to the higher 

integration and speed of today’s computer 

processors and some truly innovative 

thinking. Measuring, modeling, and manipulating how we view cancer through 

networks, not individual components, is 

possible, in part, because of highly sensitive and groundbreaking technology. 

using a concept similar to forecasting 

the weather, but considerably more complex, vito quaranta, M.D., director of
18 T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T

vanderbilt university’s integrative Cancer 

Biology Center, and colleagues developed 

a computer model that simulates tumor 

growth. The model predicts that a harsh 

microenvironment, such as that created by 

chemotherapy drugs, causes more aggressive, invasive cells to dominate, increasing the chance of metastasis. in the model 

each time a cell divides, researchers can 

randomly pick from a set of 100 different 

“phenotypes” – behaviors that result from 

distinct genetic characteristics, such as 

traits that allow it to divide more quickly. 

The environmental conditions, such as the 

level of oxygen and the characteristics of 

the microenvironment, are set by the researchers. “What we get is a picture of 

cells that are evolving and growing within 

a microenvironment,” said Dr. quaranta. 

“The nice thing about computer simulations is you can create ‘what if’ scenarios: 

what if we make the oxygen very high, 

what if we turn oxygen off in the middle 

of tumor growth, what if we change the 

landscape of connective tissue.” The longterm goal of this research is that, with the 

tools of mathematical modeling and computer simulation, physicians will be able 

to determine the best drugs to treat each 

stage of a patient’s cancer. 

in the coming years, NCi will more fully 

integrate diverse scientific fields of study 

into our current cancer research agenda, 

as clearly, we’re already learning a great 

deal from our colleagues across the scientific universe.

iNvesTiNG More DeePlY iN sYsTeMs BioloGY 

WoulD require $40 MillioN.

Subcellular Imaging

residing inside the cell’s nucleus, the genome is, we have discovered, highly organized. The positions of many genes and 

genomic regions change during physiological processes, and those changes may 

provide the earliest foreshadowing of cancer development.

That remarkable knowledge comes from 

imaging that has moved far beyond the 

realm of the diagnostic. advances in imaging devices and contrast agents used to 

improve image quality are revolutionizing 

how cancer researchers look inside cells 

and, consequently, think about cancer di

agnosis and treatment. 

“We’re at a point where we now understand the fundamental concepts, the fundamental principles by which genomes 

are organized in the nucleus, and i would 

argue, even the principles by which genomes function,” said Thomas Misteli, 

Ph.D., the head of NCi’s Cell Biology of 

Genomes group in the Center for Cancer 

research. The next step, said Dr. Misteli, 

“is to link some of these morphological 

observations to function, to physiology, 

and to disease.” 

Technological breakthroughs combined 

with advances in computational analysis of imaging data have driven the field 

dramatically forward. it has now become 

possible to visualize nuclear processes and 

movement of gene loci in single living 

cells, and generate spatial maps of how 

genomes are organized in the nucleus. 
T h e N a T i o N a l C a N C e r i N s T i T u T e N NC iN T T T 19

“This is an area of research that five or six 

years ago, literally nobody in the united 

states worked on because it was extremely 

high risk,” explained Dr. Misteli. “i came 

to NCi because it provided a lot of freedom to do high-risk research, which is 

increasingly more difficult in the outside 

[research] world.”

sriram subramaniam, Ph.D., of the laboratory of Cell Biology in NCi’s Center for 

Cancer research, recently published research using electron tomography to visualize the way hiv enters and infects cells. 

“We can enter structures in their native, 

physiological context and essentially...

zoom into cells, increasing the magnification to a point where you can actually see 

the atoms and molecules,” said Dr. subramaniam. “although you cannot do this 

with a single microscope, the combination 

of things we are doing experimentally and 

computationally has the end effect that we 

are literally walking into these viruses and 

cells at resolutions that are close to looking 

at these structures and molecules directly.”

“Previous research showing how hiv 

interacts with immune system cells and 

antibodies has been important in vaccine 

design,” said Dr. subramaniam. “however, 

understanding the complete structure of 

the viral spike may reveal other vulnerable 

targets. This knowledge will be crucial to 

solving the puzzles associated with strategies at the heart of virus invasion.”

DeveloPiNG NeW, eNhaNCeD iMaGiNG Tools 

WoulD require $150 MillioN.

“previous research showing how hIV interacts with immune system 

cells and antibodies has been important in vaccine design.”

— SrIrAM, SUbrAMANIAM, ph.d.
20 T h e N a T i o N a l C a N C e r i N s T i T u T eTi N NT N C

Cancer and Aging 

Cancer and aging are inextricably linked, so the study of specific aging syndromes has 

the potential to lead to clues about various aspects of cancer. recent research by 

the laboratories of paola Scaffidi, ph.d., and thomas Misteli, ph.d., show that cells 

affected by hutchinson-gilford progeria Syndrome (hgpS), a disease associated with pre

mature aging, can be made healthy again. Using specially modified segments of dNA, the 

scientists reversed the abnormalities seen in hgpS cells by correcting defects associated 

with a key protein. 

hgpS is a rare inherited disease affecting about one in eight million children. While appearing normal at birth, infants with hgpS age rapidly after their first 18 months, and physical 

symptoms include stunted growth, loss of hair and body fat, joint stiffness, osteoporosis, 

and heart problems. 

the genetic basis for hgpS is a single mutation in the gene encoding lamin A, a critical 

structural protein in the cell’s nucleus. Without lamin A, the nuclei of progeria cells become 

wrinkled, misshapen, and unable to function normally. experiments showed that “in order 

to achieve a potential therapeutic effect, we needed to completely eliminate the mutant 

protein,” said dr. Scaffidi.

Misteli and Scaffidi designed a chemically stable dNA sequence that the cell wouldn’t be 

able to degrade, which would bind to the mutant gene splice site in rNA transcribed from 

the defective gene. the resulting dNA-rNA complex prevents the splicing machinery from 

cutting the rNA in the wrong place. “you can think of it as a molecular band-Aid ,” said ®

Misteli. the researchers inserted their bandage into the progeria cells and observed that 

after four days almost all the mutant lamin A rNA had been eliminated and replaced with 

the properly spliced counterpart. 

“It’s amazing that we could take a cell that looked about ready to die, and a few days later it 

was healthy and ready to divide again,” said dr. Misteli. 

one of the unique features of hgpS is the absence of tumors; most other premature aging 

diseases are characterized by high tumor volume. Consequently, the researchers are cur

rently exploring whether hgpS will be a useful model system for finding the molecular links 

between aging and tumor formation.

tom Misteli, ph.d., 

head, Cell biology of 

genomes group , NCI
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 21

Bringing the Physical Sciences to Cancer

a problem as complex as fighting the constellation of diseases that make up what 

we collectively call cancer should always 

welcome new ideas, perspectives, and 

approaches. 

in workshops throughout 2008, NCi assembled groups of biologists, physicists, 

chemists, and others to come up with new 

scientific approaches to age-old quandaries. Biologists, for example, are familiar 

with complex changes in cell biology, while 

physicists can apply their knowledge of 

how discrete entities interact to a system 

where millions of cells are bumping into 

each other in the tumor microenvironment. 

Chemists understand the reactive potential 

of carcinogens and can bring a knowledge 

of that reactivity to yield a better understanding of the cancer initiation process.

at an october 2008 NCi-sponsored meeting on the physical sciences in oncology, 

Philip leDuc, Ph.D., associate professor of 

mechanical and biomedical engineering at 

Carnegie Mellon university, discussed cellular decision-making processes from a mechanical perspective. “Two important areas 

[of interest to us] are signal integration – 

how does a system respond to two distinct 

signals – and noise. Noise can be a reason a 

system functions well, as perturbations can 

help maintain system functionality as seen, 

for example, in dormant cancer cells.”

Princeton university biophysicist robert austin, Ph.D., notes that physics has 

evolved as a discipline and that physicists 

have learned to work with more and more 

complex systems. “We started out working 

with hydrogen atoms, very simple things, 

but we are now learning how to work with 

complex multi-bodied problems,” he said. 

“so i think it’s sort of natural for a physicist 

to go over into this area here because cancer, in my mind, is a very complex multibodied interaction phenomenon.”

Physicists can bring to cancer their insights 

on the properties of matter, including the 

study of time, energy, heat, and even the 

evolution of cells. Paul Davies, Ph.D., 

director of BeYoND: Center for Fundamental Concepts in science at arizona 

state university, even posits there may be 

significance in the fact that cancer cells are 

“squishy.”

“This is obviously something rather basic and yet it seems to me that it is not 

fully understood. Wouldn’t it be nice if 

we could cure cancer just by making those 

cells a bit stiffer? it just might be a matter of giving them some glue or something 

and making them stiffer and stickier – 

maybe something that would change their 

mechanical properties...”

While theoretical physics is not a field normally associated with cancer research, the 

field of biophysics is not new to NCi. The 

institute has a structural Biophysics laboratory that focuses on solution structural 

biology and biophysics aimed at understanding and regulating the mechanism of 

action of proteins and nucleic acids. The 

laboratory has a very strong interdisciplinary drug design effort, which encompasses synthetic and mechanistic chemistry, structure-based design and modeling, 

confocal microscopy, and biochemical and 

biological mechanisms. 

aDDiNG a NeTWorK oF CeNTers For The 

sTuDY oF The PhYsiCal sCieNCes aND CaNCer 

WoulD require $50 MillioN.
22 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

Dr. Robert Austin and the Physics of Cancer

robert Austin has spent his career looking at the community aspects of physics and 

how that relates to biological processes. he hopes to bring some of this community 

perspective to the field of cancer research. “the communal aspect of the way organisms responded to stress really surprised me and so I began to think about cancer in terms 

of communities and their response to stress,” dr. Austin said.

In his lab, he started building micro-habitat patches, “which are complex microenvironments. We discovered that bacteria responded in the microenvironment in a much different 

way than you would expect from just culturing them in a test tube. We’re realizing that the 

microenvironment around a cell in your body is very, very important and so I felt there was 

a connection between what I could do for making microenvironments and maybe trying to 

understand the way a cancer cell responds to its own microenvironment.”

“I think treating cancer as a disease may be the wrong approach. take, for instance, antibiotics. What bacteria have done when you try to kill them is simply evolve their way around 

the antibiotic and do it very rapidly in response to the stress that the system has put on it, 

and cancer does the same thing. So that approach of trying to kill the cancer may be exactly 

the wrong thing to do; it just turns on the evolution machine, if I could use that word, and it 

starts to mutate evermore rapidly to get around that stress.” 

“you can live with a tumor. It’s the transition from a tumor which is not invasive to one that 

is metastatic, which is an invasion. If we could learn to just keep this tumor intact, reasonably well fed, and not under stress so it’s under no evolutionary push to try to escape where 

it finds itself in trouble might be a more useful approach than trying to kill it or destroy it. 

Actually feed it, which sounds nuts, but that might actually be a better way to go about it.”

“I think physicists and other people are receptive to the idea that evolution is a very dynamic 

thing that’s turned up and down in response to stress, maybe in direct ways. that’s a pretty radical statement, but it may be true. So, physicists like that because they have no preconceptions.”

Conclusion

NCi’s cancer research portfolio is vast and complex, delving into the collection of diseases 

we call cancer through many different avenues of study. importantly, cancer research benefits the study of dozens of other diseases, for research in cancer greatly informs science’s 

understandings of human biology, in the healthy person and the patient. likewise, given 

its burden and impact, cancer affects the entire healthcare system, so NCi’s work can lead 

in many healthcare management areas, just one of which is the adoption of electronic 

medical records. The next section of this publication will delve into many of the ways 

NCi strives to put its science to work for patients.
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 23

NCI’s drug development 

platform

Clearly, we are in a new genomic era of science. Laboratories are generating and discovering 

new knowledge about cancer at a pace never before seen. Yet, for a cancer patient, we must 

provide much more than new knowledge. Cancer patients want solutions. They want therapies 

that are effective and free of debilitating side-effects. They want earlier detection. They want 

comprehensive answers to a complex problem. Through our knowledge of genes, proteins, and 

pathways, NCI is demonstrating true and lasting value, when measured in lives extended, lives 

saved, and lives spared the immense burdens of cancer. The pages that follow discuss NCI’s 

vision of a unified platform of efforts to utilize its second-to-none resources in developing 

new, safe, and effective drugs.
24 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

To advance NCi’s mission of bringing 

novel therapies to patients – and to more 

fully exploit its expertise in the later stages 

of preclinical development – NCi is focusing efforts and resources on the identification of drug candidates and on ways to 

enhance the entry of early-stage drug candidates into the therapeutics pipeline. 

The path from discovery to a new drug 

necessarily begins with establishing which 

opportunities to pursue. The virtual avalanche of genome-wide association studies and the genomic information about 

tumors that has begun to spring from The 

Cancer Genome atlas project will overwhelm our capacity to study new targets. 

Consequently, it will be necessary to review new findings and come to agreement 

on which concepts should rapidly move 

into the process of further refinement. 

NCi will require great scientific minds to 

help us make the most important choices.

NCi has state-of-the-art resources that 

span candidate identification through firstin-human testing. These unique resources 

and programs may offer technologies and 

capabilities that few universities or private 

sector entities have at their disposal. NCi 

must, in fact, become a better facilitator of 

their work, helping to reduce barriers and 

to provide developmental assistance. additionally, NCi’s intramural scientists will 

continue to develop and test new therapies for rare cancers, which tend to draw 

lesser interest from industry.

High-Throughput Screening

an important tool to identify potential 

drug targets is high-throughput screening, which allows researchers to quickly 

conduct millions of biochemical, genetic, 

or pharmacological tests. using this sophisticated, automated process, involving 

robotics, complex software, and sensitive 

detection methods, scientists can identify 

active compounds, antibodies, or genes 

involved in a particular biochemical pathway that may lead to cancer. This approach 

runs a screen of a potential target against 

individual or mixtures of known synthetic 

or natural compounds that may bind to or 

alter the function of the target. identifying 

compounds that interact with the target 

provides a starting point for drug discovery and design, and for understanding the 

role of a particular biochemical process in 

cancer.

NCi’s Molecular Targets Development 

Program (MTDP) is working to identify 

and evaluate molecular targets that may 

be candidates for drug development. as 

the centerpiece of the Center for Cancer research’s high-throughput efforts, 

the MTDP develops and evaluates highthroughput screening assays, evaluates 

screening results from libraries of natural products and synthetic compounds, 

and aids scientists in the identification of 

molecular targets and the development 

of screening tests for molecules that interact with these targets. in collaboration 

with NCi’s Developmental Therapeutics 

Program, the MTDP provides collections 

of compounds for screening to other researchers. The MTDP has also begun 

depositing screening data for more than 

100,000 publicly available compounds 

into the Nih roadmap project, PubChem. 

This allows the data to be cross-correlated 

with data on the same compounds from 

other sources and should prove to be of 

great utility to many researchers in the 

near future. 
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 25

Chemical Biology Consortium 

When its Chemical Biology Consortium 

(CBC) is up and running, NCi will have 

the capacity to bring the skills of hundreds of synthetic and medicinal chemists 

to bear on a singularly challenging problem. Designed to accelerate the discovery 

and development of effective, first-in-class 

targeted therapies, the CBC will choose 

high-risk targets that are of low interest 

to the pharmaceutical industry. To take a 

hypothetical example, a natural product 

might, theoretically, show effect in targeting a gene revealed by a characterization 

study to be defective in esophageal cancer. 

The CBC could rapidly deploy resources 

in order to synthesize that natural product. CBC chemists might also work on 

ways to make new compounds water soluble, re-engineer investigators’ assays into 

high-throughput screens, review data and 

design optimized analogs, select promising 

candidates based on established development milestones, and promote candidates 

with targeted activity to the clinic. 

The process for accomplishing CBC goals 

is largely based on the drug discovery 

strategy used by the pharmaceutical industry, but dedicated to studies of those 

new targets that might otherwise not be 

developed.

“There have been some dramatic changes 

in the past five to seven years in the way 

the chemistry and the screening is done, to 

optimally define and develop probes and 

then drugs from probes when one discovers a new target,” said James h. Doroshow, M.D., director of NCi’s Division 

of Cancer Treatment and Diagnosis. “We 

believe there is this need for us to help 

facilitate the drug discovery process by 

providing resources to chemists and biologists who can help work with their own 

molecules or take molecules in from other 

academic investigators and help speed the 

development of not just probes, but eventually drugs that can move along through 

the pipeline,” he said.

The long-term vision of the CBC is to 

bridge the gap between basic scientific investigation and clinical research supported by the NCi, as a first step in reinforcing 

the NCi as a world leader in the area of 

innovative cancer therapeutics discovery.

DruG DeveloPMeNT iNFrasTruCTure 

eNhaNCeMeNT Will require aN aDDiTioNal 

iNvesTMeNT oF $150 MillioN.

“there have been some dramatic changes in the past five to seven years in the 

way the chemistry and the screening is done, to optimally define and develop 

probes and then drugs from probes when one discovers a new target.” 

— JAMeS h. doroShoW, M.d. 
26 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

Rapid Access to Intervention 

Development Program

among its many resources, NCi has deep 

experience in the pre-clinical development 

of drugs, biologics, and vaccines – from 

toxicity testing, to pharmacodynamics, histopathology, and the production of materials that meet FDa Good Manufacturing 

Practice standards for testing in humans. 

launched in 1998, NCi’s rapid access 

to intervention Development (raiD) program makes those formidable resources 

available to academia, providing a bridge 

between discovery of a new agent and its 

introduction into Phase 0 or Phase i human 

clinical trials. Drug company scientists may 

have such services at their disposal, but 

many academic researchers do not. 

in addition, raiD supports principal investigators who are working on rare diseases and pediatric malignancies, and who 

are attempting to validate new therapeutic 

targets. The raiD program is currently 

developing significant upgrades, including 

mentoring and training for principal investigators, regulatory assistance in the filing 

of investigational New Drug applications 

with the FDa, and even conducting initial 

clinical trials at the Nih Clinical Center. 

To better enable the success of the research 

projects it supports, the raiD program is 

establishing a business model approach 

– complete with firm timelines, developmental milestones, and regular reviews to 

make important go or no-go decisions on 

research projects.

so far, the raiD program has approved 

133 projects which resulted in 21 small 

molecule and 25 biologic investigational 

new drug approvals. The raiD program 

was instrumental to the efforts of leisha 

emens, M.D., Ph.D., of Johns hopkins 

university as she began a clinical trial of 

a breast cancer vaccine for patients with 

metastatic breast cancer. raiD support 

included formulation, packaging, and release-testing of three peptides. Five hundred vials of material were produced, 

quality-control tested, and shipped to Dr. 

emens so that her team could begin vaccination. early results in six patients revealed evidence of vaccine-activated immunity in at least four patients.

Clinical Research

NCi’s mission includes extensive funding 

and conducting of clinical research. The 

institute supports a vast array of clinical 

trials designed to test new ways to treat, 

prevent, detect, or diagnose cancer – as 

well as new methods to improve cancer 

patients’ quality of life. 

The trials NCi supports take place at the 

Nih Clinical Center and in many outside institutions, including hundreds of 

academic or private hospitals, NCi-designated Cancer Centers, NCi Community 

Cancer Centers, and community-based 

medical practices located in the united 

states, Puerto rico, Canada, and worldwide. This research has helped save or extend the lives of people everywhere.

NCi enrolls thousands of people in more 

than 150 clinical trials at the Nih Clinical Center each year. home to a variety of science programs and scientists at 

many of the 27 institutes and centers that 

make up Nih, about 40 percent of the 

Clinical Center’s activity is comprised of 

studies conducted by the NCi intramural 

program. a large presence at the Clinical 

Center provides unique opportunities for 
The NaTioNal CaNCer iNsTiTuTe NT N C TTTi N 27

NCi to add to its valuable resources and 

commitment to patient care. 

For example, NCi’s Pediatric oncology 

Branch led partnerships that facilitated 

several therapeutic advances first tested 

in children at the Nih Clinical Center. 

among them was the first use of gene 

therapy, development of volume photography to measure growth of neurofibromatosis-1 tumors, and even the first multiinstitute hospital unit designed specifically 

for children at the Nih Clinical Center.

Beyond the Nih campus in Bethesda, NCi 

coordinates a network of NCi-designated 

Cancer Centers, which are principally 

based at our country’s major research universities. These centers play a vital role 

in both basic and clinical research. More 

than half of the extramural researchers 

funded by NCi work in NCi-designated 

Cancer Centers. at several NCi-designated Comprehensive Cancer Centers, for example, scientists are involved in research 

to develop novel methods that make use 

of genomic technologies to guide the 

chemotherapy choices of oncologists, by 

helping them determine the right drug for 

a particular patient, based on the patient’s 

genomic profile. ongoing clinical trials 

are studying the use of genomic signatures 

to guide therapy for breast, ovarian, and 

other cancers at a number of Comprehensive Cancer Centers. 

The 63 NCi-designated Cancer Centers are 

often referred to as crown jewels. importantly, the directors of the NCi-designated 

Cancer Centers recognize that changes are 

happening across biomedicine, and they 

are determined to contribute. in a recent 

report, the directors wrote that “advances 

in treatment will come from understanding the molecular causes of disease and 

using combination treatment approaches 

employing multiple modalities.” That 

report, “accelerating successes against 

Cancer,” contains recommendations on 

goals for NCi and the Cancer Centers 

to pursue, centering around prevention, 

early detection, treatment, survivorship, 

collaborations, and the dissemination of 

cancer control best practices. NCi is actively engaged in the implementation of 

those recommendations in consultation 

with the Centers. 

Yet, we also realize that approximately 85 

percent of cancer patients receive care in 

the communities where they live. receiving 

treatment at a world-class cancer center is, 
28 T h e N a T i o N a l C a N C e r i N s T i T u T eTi N T N N C

for too many, not an option. Frailty, age, 

language capacity, distance, and insurance limitations often keep patients close 

to home. NCi is deeply involved in fixing 

that problem, through its NCi Community Cancer Centers Program (NCCCP) 

that is studying, in a three-year pilot, how 

best to deliver state-of-the-art care and 

clinical research to patients in their local 

communities. importantly, the 16 NCCCP 

sites are also focusing nearly half of the 

resources from this program on overcoming the disparities that lead to intolerable 

differences in cancer outcomes.

“NCi’s Community Cancer Centers Program is about bringing things closer to 

home. it’s having the technology and infrastructure in place so our patients in 

Montana can get NCi Cancer Center level 

of care and access to clinical trials without 

having to go live in Denver or seattle,” 

said Dr. Tom Purcell of the Billings Clinic 

Cancer Center, an NCCCP pilot site.

exPaNDiNG The NCi CaNCer CeNTers 

ProGraM WoulD require aN aDDiTioNal 

$120 MillioN.

Reforming Clinical Trials

a linchpin of any effort to improve drug 

development must be improvements in the 

way science tests new therapies. a large 

part of today’s clinical trials system is an 

antiquated one, built around the study of 

one agent, one hypothesis at a time. it has 

become clear that a future with multi-agent 

therapies will demand a better testing system. in 2005, NCi received the final report 

from its Clinical Trials Working Group, 

and has been hard at work implementing 

many of its recommendations. This task 

requires the collaboration of the FDa, the 

Centers for Medicare and Medicaid services, industry, and academia. Yet, despite 

the hurdles, NCi is the ideal leader of this 

effort, as a facilitator and honest broker 

between all parties. 

in its own studies, NCi has been a pioneer 

in the development of so-called Phase 0 

(zero) clinical trials, which help researchers and industry make smarter decisions 

about which experimental agents should 

move into more extensive human testing. 

“This new approach has already demon-
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 29

strated its ability to significantly shorten 

the drug discovery process,” said Jerry 

Collins, M.D., director of NCi’s Developmental Therapeutics Program.

Phase 0 clinical trials – the first of which 

was conducted at the Nih Clinical Center 

in 2007, along with abbott laboratories 

– use very low doses of an investigational 

drug in just a few patients, to determine 

whether the drug is likely to be biologically effective and a good candidate to advance to later phase human clinical trials, 

or if development should be halted before 

the expenditure of hundreds of millions of 

dollars and years of work.

earlier testing of promising compounds 

in Phase 0 trials should lead to a better 

understanding of their molecular mechanisms of action, provide a closer approximation of what a safe but potentially 

effective starting dose will be, and help 

decrease the failure rates in late-stage oncology drug development. NCi estimates 

that such studies can reduce drug development times by as much as one year.

“The data you generate in Phase 0 testing allows you to design a Phase i study 

that is more well-informed,” said Dr. Collins. “Now you can select doses based on 

data that show you can achieve levels in 

patients that have an impact on the molecular target and the tumor. You can more 

rationally design your later clinical trials 

based on Phase 0 results.”

reeNGiNeeriNG CliNiCal Trials WoulD require $300 MillioN.

exPaNDiNG Phase 0 earlY PharMaCoDYNaMiC sTuDies WoulD require aN aDDiTioNal 

iNvesTMeNT oF $25 MillioN.
30 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

Conclusion

everything that happens at NCi – in its laboratories and in those laboratories it supports 

across this great country – is ultimately about cancer patients: making new discoveries 

and translating new knowledge into interventions that prevent, detect, and treat cancer. 

as much as we are entering a new era of science and medicine, it is clear that we must orient NCi in a way to facilitate a certain future when cancer is a manageable disease. There 

is little doubt about where the National Cancer institute must lead. The questions that 

remain to be answered in the coming years center around the resources and, therefore, the 

time it will take to get there. 

Clinical Trial Case Study: Marker Validation for 

Erlotinib in Lung Cancer

because lung cancer has proven to be one of the more intractable cancers to treat, 

NCI recently launched a large national clinical trial for non-small cell lung cancer 

to validate whether a biomarker can predict clinical benefit in the treatment of the 

disease. the biomarker would identify a target known as epidermal growth factor receptor 

(egFr). this receptor can be increased in some lung cancers due to the presence of extra 

copies of its coding gene. these extra copies can result in activation of tumor growth, so 

drugs that block this activation could have a significant impact on lung cancer treatment. 

the study, called MArVeL (Marker Validation for erlotinib in Lung Cancer), is also important 

because of its collaborative nature. “the MArVeL trial is unique and an important first because it is an outgrowth of specific NCI initiatives designed to advance lung cancer therapies 

and received broad input from the FdA, NCI cooperative groups, the biomarker industry, and 

the pharmaceutical industry,” said Alex A. Adjei, M.d., ph.d., senior vice president of Clinical 

research at roswell park Cancer Institute in buffalo, N.y., and chair of the study.

both egFr-positive and egFr-negative patients will receive either erlotinib (tarceva®) or 

pemetrexed (Alimta®) after they have received their initial, standard chemotherapy. erlotinib specifically targets egFr, whereas pemetrexed blocks tumor cell growth by another 

mechanism.

It is hypothesized that erlotinib will be superior in the patients with egFr-positive lung 

cancer, whereas pemetrexed would be favored in patients with egFr-negative lung cancer, 

based on knowledge from earlier, smaller studies. As with most newer trials that NCI currently supports, MArVeL will incorporate genetic studies that should help identify patients 

with different sensitivity and toxicity profiles to these therapies. 

MArVeL is the outcome of a unique and innovative collaboration, formed in 2006 between 

NCI, the FdA, and the Centers for Medicare and Medicaid Services, called the oncology 

biomarkers Qualification Initiative. the initiative was designed to qualify biomarkers for use 

in clinical trials and, ultimately, to speed better agents to cancer patients. 
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 31

building the right kind of 

NCI for the Future

The National Cancer Act of 1971 gave NCI a number of unique responsibilities and authorities. As the leader of the National Cancer Program, NCI is the principal agency for support 

of cancer research in the United States. This mission makes NCI not simply a funding source, 

but a convener and a facilitator of scientists from government, academia, and industry, whose 

mutual understandings and collaborations will be part and parcel of medicine’s future. It is, 

however, a difficult time for such an agenda, as it is for every aspect of our country’s economy. NCI’s budget remains nearly flat; once biomedical inflation is factored in, that budget 

has effectively diminished by a little more than three percent for each of the last five fiscal 

years. Nothing will stop NCI from its lifesaving efforts, and we work each day to make sure 

the Institute wisely spends every dollar. However, were NCI to receive an infusion of funding, 

NCI would carefully and thoughtfully spend those dollars, in an effort to, first, rebuild 

America’s research infrastructure capacity and then to accelerate the pace of our research 

efforts and progress.
32 T h e N aT i o N a l C a N C e r i N s T i T u T e

Building Capacity

in the years since the doubling of the Nih 

budget (in fact, about an 85 percent increase for NCi over five years, not considering medical inflation), we have learned that 

building a better, more effective research 

infrastructure takes time, careful planning, 

and ongoing support. NCi’s portfolio is a 

complex mix of thousands of contracts and 

grants to outside researchers, combined 

with the support of the hundreds of scientists who work in our labs on the Bethesda 

Nih campus and in Frederick, Md. We 

fund individual investigators working on 

hypothesis-driven science and large, collaborative, technology-driven projects. in 

many cases, a grant NCi funds is a fiveyear commitment of resources, which must 

be fulfilled, even if budgets are flat or go 

down. NCi has had to make the difficult choice recently of reducing the dollar 

amount of our grants, often by 25 percent 

or more. The result has been labs that have 

reduced the scope of their research and labs 

that have reduced staff, or taken on fewer 

young investigators.

Consequently, NCi’s first job, were it to 

receive more funding, would be to help 

increase america’s research capacity in 

several areas:

•	 Funding scientists. in academic cancer research, obtaining tenure is most 

often tied closely to getting – and renewing – an NCi grant. We have an 

obligation to help young investigators 

navigate the arduous grant application 

process and make sure their academic 

homes have mentoring committees in 

place. We must strive to assure that 

new faculty members are not just adequately funded for their research, but 

that they are primed for success from 

the outset.

aDDiNG NeW iNvesTiGaTors aND BuilDiNG 

CaPaCiTY To aTTaCK researCh ChalleNGes 

WoulD require $30 MillioN.

•	 Fostering the next generation. Much 

has been discussed in recent years 

about the graying of america’s scientific workforce, and the dearth of great 

new scientific minds entering cancer 

research. We must work, in every way 

possible, to foster scientific careers, to 

increase diversity among the scientific 

workforce, to advance scientific education and to make research a rewarding career that will keep our cancer 

research labs focused and thriving. 

exPaNDiNG researCh TraiNiNG 

oPPorTuNiTies WoulD require 

$30 MillioN.

•	 Supporting technology. The equipment 

necessary to conduct high-volume 

genomic sequencing has become faster, 

even as it has greatly fallen in price. in 

time, most physicians will have each 

patient’s complete genetic profile available. until that day comes, however, 

whole-genome sequencing, characterization, and analysis remain outside 

the capacity of most researchers. For 

just that reason, NCi envisions several 

strategically placed genomic research 

centers that could serve the entire research community.

esTaBlishiNG CerTiFieD, CeNTralizeD 

TuMor CharaCTerizaTioN laBs WoulD 

require $30 MillioN.
The NaTioNal CaNCer iNsTiTuTe 33

•	 Supporting research infrastructure.

in the early years of this century, as 

research universities received large increases in their funding from NCi and 

Nih, the construction crane was a common site on hundreds of campuses. in 

the years since, as research funding has 

flattened, many of those structures are 

underused and ill-equipped. Greater 

NCi funding will, indeed, help universities hire more research faculty; those 

dollars will also help fulfill the physical 

capacity of research institutions.

reBuilDiNG sCieNTiFiC iNFrasTruCTure aND 

TeChNoloGY WoulD require $285 MillioN.

The cancer Biomedical Informatics Grid

The technologies of 21st century cancer 

research are generating virtual mountains 

of data. as the collection of genomic data 

becomes the norm in medicine, it will 

be necessary to confront a wide range of 

issues, from the protection of patient privacy 

to the timely sharing of large volumes of 

research data to the management of clinical trials across many participating institutions. NCi’s cancer Biomedical informatics Grid 

(caBiG®) came into existence to tackle 

these and other challenging issues. caBiG 

is, first and foremost, about connections – 

between NCi researchers, cancer centers, 

Community Clinical oncology Program 

participants involved in clinical trials, cooperative groups that conduct trials on 

NCi’s behalf, and participants in the NCi 

Community Cancer Centers Program. it 

is, in many ways, an internet for cancer 

research, an organized grid, with strict 

protections of patient information and 

carefully monitored access to research 

data. caBiG is also a suite of software 

applications designed to help manage 

clinical trials, integrate disparate elements 

of cancer research, share data, and establish 

common vocabularies. caBiG is also serving 

as a public model for the development of 

electronic medical records, which will be a 

necessity in a data-driven era of medicine. 

caBiG is not simply an NCi program. it is a 

collaboration of more than 800 individuals 

from more than 80 organizations working 

on a wide variety of projects. That spirit 

of collaboration is now finding a new and 

broader home in a bioinformatics grid for 

healthcare, the BiG health ConsortiumTM, 

a recently launched effort to bring together public and private healthcare and information technology leaders, to model new 

approaches in which clinical care, clinical 

research, and scientific discovery can be 

electronically networked.

“personalized medicine is all about information. but for information 

to be useful, it has to be accessible.

— keNNeth bUetoW, ph.d.
34 T h e N aT i o N a l C a N C e r i N s T i T u T e T N N C i N TT T

speaking to the urgent need for interoperability, Kenneth Buetow, Ph.D., leader of 

caBiG, said, “Personalized medicine is all 

about information. But for information to 

be useful, it has to be accessible. What we 

are doing with caBiG is facilitating accessibility through interoperability, essentially 

creating an environment where information can be exchanged, integrated, and 

acted upon. The BiG health Consortium 

is a logical next step, to build upon what 

we have learned from caBiG and broaden 

our scope, by listening to the most important voices in healthcare.”

exPaNDiNG caBiG aND lauNChiNG The 

BiG healTh CoNsorTiuM Will require 

aN aDDiTioNal $100 MillioN.

Advanced Technology 

Partnerships Initiative

NCi’s advanced Technology Partnerships 

initiative (aTPi) is about taking a proactive 

approach to accelerate progress against 

cancer, not just by funding and conducting research, but also by establishing the 

platforms – in this case, state-of-the-art 

technology and drug development platforms – to turn that research into effective 

interventions as quickly and efficiently as 

possible. 

in November 2008, NCi took part in a 

ground-breaking ceremony in Frederick, 

Md., for a new research facility that will 

play a major role in advancing the goals of 

the aTPi. This groundbreaking was truly 

the beginning of a new era of expanded 

drug and technology development via public, private, and academic partnerships. 

The research park represents an opportunity to co-locate private sector research 

and development programs, biotechnology partners, and academic collaborators 

on a research campus dedicated to reducing the cancer burden. 

The aTPi will also take advantage of 

the unique capabilities of NCi’s current 

Frederick campus at Ft. Detrick. NCiFrederick is one of just 38 Federally Funded 

research and Development Centers, and 

the only FFrDC devoted solely to biomedical research. The designation allows 

NCi-Frederick to be operated by a private 

contractor, which is able to more rapidly 

deploy resources than a purely governmental entity. using the FFrDC capabilities, the aTPi will expand collaborations 

with a variety of private companies and 

institutes to develop new agents, new 

diagnostics, and new ways of monitoring 

response to therapy – and then carry them 

forward to first-in-human studies. 

The aTPi will help provide access to cutting-edge, often costly technologies that 

are not readily available in the research 

community. Partnerships, two of which 

are already in place, will flow from access 

to these technologies and the expertise required to operate them. under the aTPi, 

for example, NCi could collaborate with 

partners to test the optimal use of new 

technologies in cancer research, or to aid 

start-up biotechnology and pharmaceutical companies that have received small 

business grants by providing the expertise and equipment needed to characterize 

their investigational agents or manufacture pharmaceutical-grade agents for use 

in human trials. 

What the new Frederick facility, in particular, will provide is a tremendous 

opportunity to expand training capabilities. 

With the space and expertise available 
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 35

in a single facility, NCi will significantly 

enhance its ability to teach the next generation of scientists how to use emerging 

technologies, a process that they can then 

repeat at their home institutions. “The 

new facility,” said Craig reynolds, Ph.D., 

director of the office of scientific operations at NCi-Frederick “will provide the 

physical infrastructure to carry out the 

aTPi and should help free up space on the 

Ft. Detrick campus to enhance other programs and core services that support both 

the intramural and extramural cancer research community.”

Biobanking

Groundbreaking efforts such as GenomeWide association studies and TCGa 

depend heavily on the quality of their specimens, which must be obtained, staged, annotated, stored, and distributed according 

to the highest standards. organizing those 

tasks, on a national level, falls to NCi’s 

office of Biorepositories and Biospecimen 

research (oBBr).

Considerable variability exists in the collection, processing, storage, and annotation of the majority of human specimens 

available for research. To solve this critical problem, NCi is leading an effort to 

ensure that human biospecimens available for cancer research are of the highest quality. The first step was development 

of the NCi Best Practices for Biospecimen 

resources, a document that spelled out 

procedures for standardizing biobanking 

practices and operations. The second stage 

is to develop and implement state-of-thescience data-driven procedures to provide 

human biospecimens that have molecular 

integrity and clinical relevance for cancer 

research and treatment. 

oBBr’s director, Carolyn Compton, M.D., 

Ph.D., and her staff are currently developing the concept for a new national 

biobank: a unique, non-profit public resource that will ensure the adequate and 

continuous supply of human biospecimens 

and associated measurable, high-quality 

data, all acquired with the highest ethical 

standards.

Carolyn C. Compton, 

M.d., ph.d., director, 

office of 

biorepositories 

and biospecimen 

research , NCI
36 T h e N a T i o N a l C a N C e r i N s T i T u T eTi N NT N C

Common Language for Clinical Trial Contracts

Clearly, the future of personalized oncology will require the use of multiple, targeted therapies 

in order to block the many pathways that cancer cells exploit to grow and spread throughout 

the body. testing combinations of such therapies in human clinical trials, however, has proven to be a daunting task. Such trials often involve collaboration between several companies, each 

of which has intellectual property concerns. dealing with such issues and hammering out contract 

details often leads to long delays, if not complete derailment, of clinical trials. 

NCI’s leadership, as a broker between the public and private sectors, is helping break the logjam of 

lengthy and costly contract negotiations for partnerships between the pharmaceutical industry and 

academic research institutions, including NCI-designated Cancer Centers. this came about through 

NCI’s participation in the Ceo roundtable on Cancer, a unique group of corporate Ceos, academic 

research presidents, and other leaders from 42 organizations. 

“NCI’s involvement with the Ceo roundtable since its inception in 2001 has been critical,” commented the group’s chief operating officer, Martin J. Murphy, Jr., ph.d. “We pledged to shorten the 

time for industry-academic partnership negotiations from as much as 300 days down to 30 days...but 

it couldn’t have happened until NCI got involved.” 

dr. Murphy credits NCI’s leadership for recommending that the Ceo roundtable establish a Life Sciences Consortium (LSC) made up of roundtable members from the pharmaceutical, biotechnology, 

and academic research communities. the goal of the LSC is to “look into the pre-competitive space 

where there are problems common to all members of the Consortium,” dr. Murphy said.

the first major impediment the LSC addressed is the length of time it takes to negotiate a clinical 

research agreement between a pharmaceutical company, which has a drug to be tested, and an 

academic institution such as an NCI-designated Cancer Center. “It currently takes anywhere from 

180 to 300 days,” dr. Murphy noted, costing companies more than $1 million a day in delays. the Ceo 

roundtable identified this as a priority issue four years ago, he recalled, but progress stalled until 

NCI leaders stepped forward in 2007, “that was the key that opened the door.”

With financial support from NCI and the Ceo roundtable, the LSC analyzed 84 clinical contracts. 

they created an online Master Agreement template of “harmonized” contract language “that will 

eliminate literally hundreds of days of back and forth negotiations,” dr. Murphy added. the Master Agreement is free for everybody to use, and is posted on Cancer.gov at http://cancercenters.

cancer.gov.

on Sept. 17, 2008, the department of Justice announced that it would “not oppose” the model contract language, which “is not likely to be anticompetitive and can be used to help increase efficiency 

in contract negotiations, potentially reducing costs and shortening the time needed to begin clinical 

trials.”

NCI, along with the LSC, will now move on to tackle issues of intellectual property rights that often 

impede public-private sector collaborations. “I applaud NCI’s leaders for doing what they do best 

– which is not only pioneering research but also in pointing the way for research to prosper in the 

future,” dr. Murphy said.
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 37

NCI’s Commitment to Its Staff

in 2008, the National Cancer institute 

qualified for the Ceo Cancer Gold standardTM. Bestowed by the Ceo roundtable on Cancer, the nonprofit organization of cancer-fighting Ceos, this award 

recognizes the commitment of companies 

and non-profit organizations to fighting cancer one employee at a time. Gold 

standard recognition means that NCi has, 

first, established and enforced tobaccofree worksite policies. in fact, the entire 

National institutes of health campus in 

Bethesda, Md., is now tobacco-free. in 

addition, the Gold standard designation 

means NCi also provides no-cost coverage for evidence-based tobacco treatments 

for employees and their family members. 

other requirements include sustaining a 

culture that promotes diet and nutrition; 

promoting physical activity; and providing prevention, screening, and early detection – along with access to quality treatment and clinical trials.

in announcing the designation, William 

C. Weldon, chairman and chief executive 

officer of Johnson & Johnson and chair of 

the Ceo roundtable on Cancer, said, “it 

is both appropriate and inspirational that 

the preventive health and wellness guidelines and unparalleled cancer care for 

which the National Cancer institute and 

its director, Dr. John Niederhuber, stand 

for are provided for NCi’s own employees and their family members who are on 

the frontlines of our nation’s battle against 

cancer each and every day.”
38 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

CreaTiNG a u.s. oNColoGY Tissue BaNK 

WoulD require $30 MillioN.

NCI’s Commitment to All

Because cancer is, in reality, not a singular 

disease but many conditions, its causes, its 

progression, and its effects vary tremendously. Despite its heterogeneity, there is 

perhaps one common trait of all cancers 

that particularly stands out: fear. virtually 

all of us fear cancer. We fear that, as we 

age, cancer may come to us. if we have 

survived cancer, we fear it may return. We 

fear that cancer may take our lives or the 

lives of those we care about. 

The National Cancer institute is, of 

course, dedicated to research. and dedicated research can help replace fear with 

hope. in the years to come, NCi will remain focused on its work and its missions 

that will, by their very nature, require 

great change.

•	 We will need to change how we think 

about cancer prevention. Choosing 

the right healthy behaviors – diet and 

exercise, for example – and avoiding 

exposure to certain environmental 

risk factors, none more important 

than tobacco, can help prevent the 

development of cancer. Yet, why one 

person will develop cancer and another will not, given the same exposures, remains largely unknown. We 

need to apply our rapidly increasing 

knowledge of both the tumor and its 

microenvironment, as they relate to 

specific organ sites, in order to find 

new targets and markers of early carcinogenic events and, additionally, to 

study transcriptional regulation and 

epigenetic changes. We must then find 

ways to take highly characterized individuals whom we have determined 

are at high risk and intervene, with 

manipulations or prevention measures, 

to mitigate their risk. We need to include earliest diagnosis as a preventive 

strategy and more deeply incorporate 

biomarkers and imaging technology 

into our prevention portfolio.

•	 We will need to change how we contemplate cancer survivorship. Cancer 

is rarely a transitory event: something 

that is dispatched with and then disappears. For a significant proportion 

of cancer patients, second, third, and 

even fourth malignancies are a linger-
The NaTioNal CaNCer iNsTiTuTe T N NC iN T T T 39

ing worry. NCi is committed to research that studies the genetics of survivorship in order to better reveal those 

individuals most at risk for new cancers 

– and then to design prevention and early 

detection protocols for each patient.

•	 We must change how we fight the 

disparities in cancer care that lead to 

unequal outcomes. Cancer does not 

discriminate, but its outcomes are all 

too frequently affected by race, ethnicity, income, age, and frailty. We must 

not allow those differences to alter 

the care we offer. as we bring cancer 

care closer to patients in their communities, through efforts like the NCi 

Community Cancer Centers Program, 

and work to reduce barriers to care 

through programs like the Community 

Networks Program, the Minority institution/Cancer Center Partnership Program, and the Patient Navigation research Program, we must ensure that 

all patients who need care have equal 

access to the latest treatments and techniques – the fruits of our latest science. 

We must also work to understand the 

genetic differences that may lead to 

different disease burdens, such as the 

disproportionate rates of prostate cancer among african american men.

•	 We must remember that research into 

the causes of cancer equals progress 

against many diseases. Cancer research studies biological processes 

at their most basic, molecular level. 

The knowledge we gain about cancer, about its growth, nourishment, 

and spread, have been shown time 

and again to have significance against 

many diseases. For example, recent 

studies show that the leukemia drug 

Gleevec may help in an array of illnesses that have nothing to do with 

cancer. among them: diabetes, Crohn’s 

disease, pulmonary arterial hypertension, rheumatoid arthritis and scleroderma and maybe even seasonal allergies. our models for cancer care also 

can lead the way for improved, less 

costly medical care – from the adoption of electronic medical records, to 

electronically interconnected hospitals and patients, and to greater use of 

evidence-based care.

Conclusion

Despite difficult economic times, the National Cancer institute must not allow the pace of 

its progress to diminish. NCi must be – and must remain – visionary. simply stated, NCi 

must lead. We must carefully consider every opportunity, and we must invest prudently 

and wisely. That guiding philosophy will never change, for it is our commitment to all 

americans.
40 T h e N aT i o N a l C a N C e r i N s T i T u T e T N NC iN T T T

The 2010 Professional Judgment Budget Request

the National Cancer Institute’s research portfolio encompasses thousands of grants it funds in universities 

and cancer centers across the United States and internationally—along with the studies conducted by a cadre 

of government scientists in the Institute’s own laboratories. the numbers you see on this page represent the 

NCI’s professional judgment on potential budget increases—additions to NCI’s research portfolio in the first 

year of increased funding—that could hasten our research progress against cancer, bringing new therapies, 

earlier detection and better prevention techniques to all people.

National Cancer Institute

New Investments 

(dollars in millions)

Increase biomedical computing capabilities 45

develop imaging tools 150

Invest in intramural program 100

expand the Cancer genome Atlas 200

establish certified centralized tumor characterization labs 30

Create a U.S. oncology tissue bank 30

Increase drug development infrastructure 150

Invest in resources – nanoparticles, proteins, and clinical proteomics 75

reengineer Clinical trials 300

expand cabIg® and launch bIg health ConsortiumtM 100

Fund early-phase pharmacodynamic studies 25

Invest in systems biology 40

raise rpg success rate and average cost per grant 340

expand research training opportunities 30

Increase the number of new investigators 30

rebuild scientific infrastructure 285

expand Cancer Centers program 120

Add a network of centers for the study of the physical sciences and cancer 50

Total Annual Increased Investment 2,100
NIH Publication No. 08-6363

Printed January 2009