3 8

5

1 6

2 7

4 9

TABLE OF CONTENTS

Investing In The Future 

Of Cancer Research

Page 1

Leading The Nation’s 

Progress Against 

Cancer

Page 4

Understanding the 

Mechanisms of Cancer

Page 12

Preventing Cancer

Page 22

Detecting & Diagnosing 

Cancer

Page 30

Treating Cancer

Page 38

Advancing Public Health 

in Cancer

Page 62

Strengthening the 

Cancer Research 

Enterprise

Page 76

Budget Proposal

Page 88
NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

INVESTING IN THE FUTURE 

OF CANCER RESEARCH

Highlights of the NCI Annual Plan & Budget Proposal for Fiscal Year 2019

Every day, scientists and physicians dedicated to cancer research work to make discoveries 

that will advance new treatments and tools into the clinic. Patients participate in clinical 

trials with the hope of finding new options for themselves and producing better outcomes 

for future patients who will face the same disease. Their combined efforts—enabled by research 

funding—have led to new ways to prevent, detect, and treat cancer and a 25% decline in the rate 

of death from cancer over the past two decades.

Despite this progress, more work remains. Nearly 40% of Americans will be diagnosed with 

cancer in their lifetimes. In 2017, cancer is expected to take the lives of about 600,000 adults and 

2,000 children in the United States. Many of us have had a family member, friend, or neighbor 

with cancer or have been affected by cancer ourselves. Continued progress requires strong and 

sustained federal investment in cancer research.

The National Cancer Institute (NCI) is the federal government’s principal agency for cancer 

research and training. NCI leads, conducts, and supports cancer research across the nation 

to advance scientific knowledge and help all people live longer, healthier lives. As the largest 

funder of cancer research in the world, NCI supports investigators to advance a broad portfolio 

of research—from laboratory discoveries to clinical trials to population sciences. NCI encourages 

collaboration between scientists and organizations, conducts a rigorous and accountable funding 

process, and works with stakeholders to ensure that the national investment in cancer research 

has maximum impact.

There is strong national support for the work NCI funds. The Cancer MoonshotSM, which aims to 

accomplish a decade’s worth of research in 5 years, is just one example of a targeted effort with 

specific resources for making dramatic advances against this disease.

NCI puts forward an annual plan and budget proposal that highlights the impact of the nation’s 

investment in cancer research and directs attention to several areas for which additional support 

will enable more progress. The stories of investigators found in this document illustrate the 

innovative research catalyzed by NCI-support, and the stories of patients and cancer survivors 

highlight how NCI’s investments in research help people live healthier lives.

1
Future of Cancer Resea rch

Research Opportunities

Building on the momentum made in the past few decades requires support for all areas of cancer research, from basic 

science to cancer survivorship. NCI’s commitment to train the next generation of cancer researchers is unwavering and 

cuts across all research areas. The Annual Plan and Budget Proposal for Fiscal Year 2019 includes funds for exceptional 

opportunities in the following research areas.

UNDERSTANDING 

THE MECHANISMS 

OF CANCER

Cancer is a complex disease 

that requires an in-depth 

understanding of how genetic, 

behavioral, and environmental 

factors contribute to its 

development. Discoveries in 

basic scientific research on the 

growth, survival, and spread 

(metastasis) of cancer cells in the 

body have been, and continue 

to be, essential for continued 

progress. Part of NCI’s mission 

is to support the basic scientific 

research that will lead to new 

ways to prevent, detect, and treat 

cancer, thereby enabling people 

to live longer, healthier lives. Two 

areas of research opportunity are 

understanding and therapeutically 

targeting the molecular drivers 

of cancer and understanding and 

finding new ways to control 

cancer metastasis.

PREVENTING 

CANCER

Improved cancer prevention 

means fewer people will face 

a diagnosis of cancer and the 

physical, financial, social, and 

psychological harms of the 

disease and its treatment. NCIsupported research informs efforts 

to minimize human exposure 

to cancer-causing agents in 

the environment and improve 

screening to detect and treat 

precancerous growths before 

they develop into cancer. An 

emerging area of opportunity is 

the development of vaccines to 

prevent not only the cancers that 

are caused by viruses but also 

cancers that are not caused by 

viruses.

DETECTING & 

DIAGNOSING 

CANCER

Early detection is a proven strategy 

for saving lives from cancer. NCI 

funds research to improve cancer 

detection in its early stages, 

when it may be most treatable, 

and to accurately assess how 

likely it is that a precancerous 

growth will progress to lifethreatening disease. An area of 

opportunity includes developing 

new approaches, including liquid 

biopsies and other less-invasive 

methods, for the early detection 

of precancers and early cancers. 

These approaches have the 

potential to increase the number 

of cancers for which we have 

clinically effective screening 

programs as well as to improve 

the technologies currently used to 

screen for cancer.

2

Find videos at plan.cancer.gov
3

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

TREATING 

CANCER

NCI’s commitment to developing 

new treatments for cancer patients 

spans basic research to discover 

the mechanisms of cancer, 

preclinical research to investigate 

the anticancer effects of therapies 

that target these mechanisms, 

and clinical research to test new 

therapies in patients. Despite 

recent advances in targeted 

therapy and immunotherapy, more 

needs to be done to substantially 

improve the outlook for both 

adults and children with cancer. 

Three areas for further investment 

include developing combination 

therapies, biomarker-guided 

immunotherapies, and precision 

medicines that target specific 

abnormalities in a patient’s cancer.

ADVANCING 

PUBLIC HEALTH 

IN CANCER

NCI supports research focused 

on improving the delivery of 

cancer care and designing 

interventions at the individual 

and population levels to improve 

cancer prevention, screening, 

treatment, and survivorship. 

Some areas of opportunity include 

understanding how body weight 

and physical activity influence 

cancer risk and outcomes; further 

reducing tobacco use; delivering 

high-quality cancer prevention, 

screening, and treatment to 

all regions of the country; and 

improving the quality of life of 

cancer survivors.

REDUCING 

CANCER 

DISPARITIES

Advances in cancer research do 

not benefit all people equally. 

Some cancer disparities can be 

attributed to differences in access 

to, utilization of, and quality of 

care, but biology and lifestyle 

factors are also important. The 

biology of cancer disparities 

requires more research and 

attention to improve the outcomes 

of patients and individuals at 

risk of cancer. Innovative ways 

to mitigate the effects of biology 

and lifestyle factors and to 

improve access to quality care are 

needed to ensure the best cancer 

outcomes for all Americans. This 

will require additional studies of 

cancer in underrepresented racial/

ethnic populations and greater 

participation by members of these 

populations in clinical trials. Special 

attention to the cancer needs of 

rural populations is also essential.
LEADING THE 

NATION’S PROGRESS 

AGAINST CANCER
5

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Groundbreaking research and training supported by the National Cancer Institute 

(NCI) has led to a substantial reduction in the burden of cancer in the United 

States. The development of improved screening and prevention methods, novel 

approaches for the diagnosis and detection of cancer, and innovative treatments have all 

contributed to this progress.

The National Cancer Institute

NCI is the federal government’s principal agency for cancer research and training. It is 

part of the National Institutes of Health, which is one of 11 agencies that comprise the 

Department of Health and Human Services. NCI leads, conducts, and supports cancer 

research across the nation to advance scientific knowledge and help all people live 

longer, healthier lives.

As the largest funder of cancer research in the world, NCI supports investigators working 

across the United States and in other countries. This support is advancing a broad 

portfolio of research—from basic laboratory science to clinical trials and population 

science—to improve our understanding of cancer and cancer prevention, diagnosis, 

treatment, and survivorship. NCI encourages collaboration between scientists and 

organizations, conducts a rigorous and accountable funding process, and works with 

stakeholders to ensure that the nation’s investment in cancer research has maximum 

impact.

The NCI Annual Plan and Budget Proposal

The National Cancer Act of 1971 authorizes NCI to prepare an annual budget proposal 

directly for the President and Congress. This proposal represents NCI’s best professional 

judgment about the funding needed to make the most rapid progress against cancer.

The Annual Plan and Budget Proposal for Fiscal Year 2019 highlights the impact of the 

nation’s continuing investment in cancer research and directs attention to several 

areas for which additional support will enable greater and faster progress. The stories 

of investigators who have devoted their careers to cancer research illustrate some of 

the innovations driven by NCI-supported science. The stories of patients and survivors 

highlight how NCI’s investments in research can improve lives and reveal challenges that 

remain to be addressed. 

As this plan shows, the research community—under NCI’s leadership—is making pivotal 

advances against cancer. However, much more still needs to be done to increase our 

understanding of the many diseases we call cancer and extend the benefits of research to 

even more people.
6

Progress Against Cance r

The Return on Cancer Research Investment

Improvements in cancer prevention, screening, and treatment, fostered 

by dedicated researchers across the nation and patients who volunteer 

to participate in clinical trials, have helped to reduce the burden of cancer 

in the United States. The clearest sign of this progress is the steady 

decline in the rate of cancer deaths, which has continued for more than 

two decades. Specifically, the cancer death rate among adults declined 

by 25% from 1990 through 2014, and the death rate among children and 

adolescents (age 19 and younger) declined by 35%. Moreover, of the top 

10 causes of death among Americans, only cancer showed a decrease 

from 2014 to 2015.

For most of the last half of the 20th century, the rate of cancer deaths 

rose sharply, driven largely by cigarette smoking. Beginning in the 

early 1990s, however, cancer death rates started to decline because of 

reductions in tobacco use, as well as increased utilization of other cancer 

prevention measures, better screening, and new treatments. Continued 

progress in these areas should ensure that the downward trend in the 

overall rate of cancer death is sustained or accelerated to prevent the loss 

of even more lives.

Another sign of progress is that the overall rate of cancer incidence for 

men and women combined declined steadily from 2007 through 2014. However, when 

the rates for men and women were analyzed separately, a decline was observed only for 

men; the incidence rate for women remained stable during this period. Nevertheless, 

these separate trends for men and women stand in sharp contrast with the rising rates of 

cancer incidence observed for both sexes before the beginning of the 21st century.

The Need for Greater Progress

The surest indicator of the need for greater progress is that an estimated 1.7 million 

new cases of cancer and 600,000 cancer deaths will occur among U.S. adults in 2017 and 

approximately 15,000 new cases of cancer and 2,000 cancer deaths will occur among U.S. 

children and adolescents. In addition, the incidence and mortality rates for some cancers, 

such as liver cancer, are still increasing, and the numbers of new cancer cases and cancer 

deaths will continue to grow as the population ages.

Cancer Disparities

Despite the overall decreases in U.S. cancer incidence and mortality, certain population 

groups in this country suffer disproportionatly from some cancers. Although many of 

the differences in cancer incidence and mortality between population groups can be 

attributed to access to cancer screening tests and quality cancer care, additional factors, 

including genetics and lifestyle factors, are also important. More research is needed to 

better understand and mitigate the effects of both biological and nonbiological factors 

that contribute to cancer disparities. 
7

9

Liver cancer is one example for which disparities 

exist. The rates of incidence and death for this 

cancer are substantially higher among American 

Indians/Alaska Natives, Asian Americans/Pacific 

Islanders, Hispanics, and African Americans than 

among whites. The reasons for these disparities 

are not clear and represent an area of research 

opportunity.

One new NCI initiative focused on understanding 

biological factors that may contribute to cancer 

disparities is the Early Onset Malignancies Initiative 

(EOMI), which was announced in 2016. In this 

initiative, researchers are seeking to understand 

why certain racial and ethnic groups have 

increased risks of developing specific cancers at an 

early age. Samples of early-onset tumors from four 

different racial/ethnic populations will be collected 

for detailed molecular analyses, along with 

information about treatment(s) received, tumor 

response, and patient outcomes. Characterization 

at the molecular level will enable researchers 

to determine if genetic factors are contributing 

to disparities in early-onset cancer among the 

different population groups. Data from the study 

may enable researchers to answer questions about 

the molecular determinants of early-onset disease 

and possible associations with treatment response 

or prognosis.
10

Progress Against Cance r

Global Burden of Cancer

Worldwide, more than 21 million new cases of cancer are predicted to occur in 2030, 

an increase of 50% over the 14 million cases that occurred in 2012. It is also predicted 

that 13 million cancer-related deaths will occur in 2030, an increase of nearly 63% 

over the 8 million cancer-related deaths that occurred in 2012. Most of this growing 

burden of cancer incidence and mortality will be borne by low- and middle-income 

countries.

To address this growing global burden of cancer and to gain knowledge that can 

be applied in the United States as well, NCI facilitates global collaborations with 

other U.S. agencies, foreign governments, nongovernmental organizations, and 

companies to support clinical trials and medical device development for use in lowresource settings.

The Cancer MoonshotSM

In 2016, NCI was afforded a unique opportunity to advance cancer research through 

the Cancer Moonshot initiative. The goals of this initiative are to accelerate progress 

in cancer research, increase cooperation and collaboration among members of the 

cancer research community and other stakeholders within and outside the federal 

government, and expand data sharing.

Under the initiative, the research community identified 10 areas of research 

opportunity where progress could be accelerated with additional funding. NCI was 

given primary responsibility for scientific oversight of the initiative.

In December 2016, Congress passed the 21st Century Cures Act, authorizing 

$1.8 billion in funding for the Cancer Moonshot over 7 years. An initial $300 million 

was appropriated in fiscal year (FY) 2017 to fund the Moonshot recommendations.

CANCER MOONSHOT RECOMMENDATIONS

A. Establish a network for direct patient involvement

B. Create a translational science network devoted exclusively to immunotherapy

C. Develop ways to overcome cancer’s resistance to therapy

D. Build a national cancer data ecosystem

E. Intensify research on the major drivers of childhood cancers

F. Minimize cancer treatment’s debilitating side effects

G. Expand use of proven cancer prevention and early detection strategies

H. Mine past patient data to predict future patient outcomes

I. Develop a 3D cancer atlas

J. Develop new cancer technologies
11

• As the largest funder of cancer research in the world, NCI invests in research ranging from basic science to clinical 

trials to population research to advance scientific knowledge and help all people live longer, healthier lives.

• These investments have led to improved cancer prevention, detection, and treatment methods and declines in the 

rates of cancer incidence and death in the United States. 

• Strong and sustained support for cancer research is necessary to make advances against this disease, both in the 

United States and worldwide.

• Increased investments in cancer research will enable us to make even greater progress.

KEY TAKEAWAYS
UNDERSTANDING 

THE MECHANISMS 

OF CANCER
13

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Cancer is a complex disease that requires an in-depth understanding of how 

genetic, behavioral, and environmental factors contribute to its development. 

Discoveries in basic scientific research about the growth, survival, and spread 

(metastasis) of cancer cells in the body have been, and continue to be, essential for 

continued progress. Part of NCI’s mission is to support the basic scientific research that 

will lead to new ways to prevent, detect, and treat cancer, thereby enabling people to 

live longer, healthier lives. Two areas of research opportunity are understanding and 

therapeutically targeting the molecular drivers of cancer and understanding and finding 

ways to control cancer metastasis. 

Identifying Molecular Changes That Drive Cancer

From the time scientists began to identify cancer-causing genes, or oncogenes, in 

humans more than 30 years ago, they began to explore the possibility that targeting 

the proteins produced by these genes might kill cancer cells or slow their growth. NCIsupported basic and clinical research validated this approach, ultimately leading to Food 

and Drug Administration (FDA) approval of drugs such as trastuzumab (Herceptin®), 

imatinib mesylate (Gleevec®), and cetuximab (Erbitux®). NCI-supported research also led 

to FDA-approvals of drugs, such as bortezomib (Velcade®), everolimus (Afinitor®), and 

dinutuximab (Unituxin®), that target other molecules in cancer cells besides the proteins 

produced by oncogenes.

Currently, more than 35 molecularly targeted therapies have been approved by FDA for 

use by cancer patients. Despite this progress, more research is needed to understand 

the mechanisms that drive cancer. This research will help to identify additional molecular 

targets, to generate “lead compounds” that act against those targets, and to advance 

candidate drugs through the preclinical and clinical development processes.

In addition, more research is needed to understand the mechanisms by which cancer 

cells develop resistance to cancer therapies, including molecularly targeted therapies, 

and how to overcome this resistance. Drug resistance is one of the main causes of cancer 

treatment failure and reduced survival for patients.

THE VISION

To have effective targeted drugs to offer patients for all molecular drivers of cancer

THE APPROACH

• Support a robust research program in the molecular understanding of cancer to 

identify new targets 

• Advance drug discovery to tackle difficult-to-target molecules
14

Understanding Cance r

Research Priorities

NCI is committed to increasing our fundamental knowledge of the inner workings of 

cancer cells to identify new molecular targets and to translate those discoveries into 

therapies that will improve the lives of cancer patients.

Discover New Molecular Targets

The genomics revolution and technological advances that followed the completion of 

the Human Genome Project have allowed researchers to molecularly characterize many 

human cancers. One important, recently completed initiative was The Cancer Genome 

Atlas (TCGA), in which the genomes of more than 30 types of cancer were characterized 

to identify genetic alterations in the cancer cells that might be targeted therapeutically. 

TCGA researchers identified thousands of genetic alterations, including many potential 

targets. FDA-approved drugs exist for some of these targets, and additional drugs that 

target other genetic alterations are in various stages of development.

NCI-funded scientists are working to fully understand the role of these genetic alterations 

in cancer development and progression, identify ways of targeting them, develop new 

molecularly targeted therapies, and, ultimately, test the therapies in clinical trials to 

determine whether they will benefit cancer patients.

Specific NCI-supported initiatives and programs in this area include:

• The Therapeutically Applicable Research to Generate Effective Treatments 

(TARGET) initiative, which focuses on identifying molecular targets in several 

aggressive hard-to-treat childhood cancers. TARGET investigators have made many 

novel discoveries, including the identification of a distinct molecular subtype of 

pediatric acute myeloid leukemia that may respond to treatment with drugs called 

JAK kinase inhibitors. (Learn more about the TARGET initiative on page 55.)

• The Cancer Target Discovery and Development Network (CTD2), in which 

researchers seek to functionally validate discoveries made in large-scale 

genomic studies that, upon further investigation, may lead to the development 

of new therapies. This validation may involve molecular and biological assays or 

computational analysis.

• The Developmental Therapeutics Program (DTP), which provides services and 

resources to academic and private-sector researchers worldwide to facilitate the 

discovery and development of new cancer therapies. Since its inception by Congress 

in 1955, DTP has supported the development of more than 40 U.S.-licensed 

cancer drugs through extensive collaborations with academic institutions and 

pharmaceutical and biotechnology companies.

• The NCI Experimental Therapeutics Program (NExT), a DTP effort that seeks to 

translate breakthrough discoveries in basic and clinical research into new cancer 

therapies while shortening the timeline for drug development. Both CTD2

 and NExT 

are intended to complement the drug development efforts of pharmaceutical and 

biotechnology companies by supporting meritorious, high-risk research. Dabrafenib 
15

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

(Tafinlar®), trametinib (Mekinist®), and nivolumab (Opdivo®) are examples of FDAapproved drugs that were developed with the support of NExT.

Target Difficult-to-Drug Molecules

Although we have successfully developed therapies that target the proteins produced by 

many oncogenes, there is still much work to be done. For example, members of the MYC

and RAS gene families are frequently altered in human cancer, but drugs that directly 

target their protein products have yet to be approved by FDA.

• The RAS gene family includes the genes HRAS, KRAS, and NRAS. Mutations in these 

genes cause more than 30% of all human cancers, including 95% of pancreatic 

cancers and 45% of colorectal cancers. Cancers that have a RAS mutation generally 

have a poor prognosis. Developing drugs that effectively target mutant RAS 

proteins is a major research challenge. In one such effort, NCI-funded researcher 

Kevan Shokat, Ph.D., of the University of California, San Francisco, generated small 

molecules that target a specific alteration in KRAS. (Read about Kevan’s work on 

page 16.)

In 2013, NCI launched the RAS Initiative to accelerate progress in this area. Under 

this initiative, researchers are exploring innovative approaches to target RAS-driven 

cancers, with the goal of finding effective therapies for patients with these cancers. 

Based at the Advanced Technology Research Facility of NCI’s Frederick National 

Laboratory for Cancer Research, the initiative brings together scientists from NCI’s 

intramural research program, academia, and biotechnology and pharmaceutical 

companies. The RAS Initiative highlights NCI’s ability to convene experts from across 

the research enterprise to address complex problems in cancer research.

• The MYC family of genes, which was discovered decades ago and includes the MYC, 

MYCN, and MYCL genes, has been shown to be a critical player in the development of 

approximately 15% of human cancers and in drug resistance to targeted therapies. 

Despite this knowledge, no drug has been developed that targets MYC proteins 

directly. However, recent work by NCI-funded researchers and others has led to the 

discovery of a promising new class of dual-action inhibitors that block the activity 

of two other proteins, BRD4 and PI3K, that are necessary for the activation and 

stabilization of MYC proteins.

This work and other recent advances in the drug discovery field have renewed 

enthusiasm for our ability to hit targets that once were thought to be “undruggable.”

KEY TAKEAWAYS

• NCI supports research to understand the molecular basis of cancer and to identify molecules in cancer cells that are 

potential therapeutic targets.

• NCI supports research to develop molecularly targeted therapies for cancer, including therapies that target yet-tobe-drugged molecules.
Understanding Cance r

KEVAN SHOKAT, PH.D.

Professor, Department of Cellular and 

Molecular Pharmacology, University 

of California, San Francisco

Professor, Department of Chemistry, 

University of California, Berkeley

Investigator, Howard Hughes 

Medical Institute

THINKING CHEMICALLY TO DISCOVER NEW TARGETED 

CANCER DRUGS

Chemical biologist Kevan Shokat brings a 

unique perspective to the development 

of molecularly targeted therapies. He began 

his research career as an organic chemist, 

only later turning to biology. He believes 

that this hybrid training enables him to 

“think chemically” but with a deep enough 

understanding of biology to know what to 

focus on in addressing major biomedical 

challenges. Importantly, he believes we 

need to unwind many of our assumptions 

about things and conduct research in an 

open-minded, open-ended way. “That will 

lead us to fundamental discoveries,” he 

said, “and, every so often, you’ll overturn 

some dogma and that will be the crack in 

the problem.”

Encouraged by pioneers in the study of 

oncogenes—altered genes that have the 

potential to cause cancer—Kevan entered 

the field of cancer drug discovery. Among 

the oncogenes he sought to target were 

members of the RAS gene family, which play 

an important role in more than 30% of all 

human cancers, including 95% of pancreatic 

cancers, 45% of colorectal cancers, and 35% 

of lung cancers. The proteins produced by 

RAS oncogenes had long been thought to 

be “undruggable” because they lack a clear 

binding site for drug attachment. Kevan, 

however, prefers to view them as “not yet 

drugged.”

With the support of NCI funding, Kevan’s 

team focused initially on a mutant form 

of the KRAS gene that occurs in nonsmall cell lung cancer. Using a technology 

that had not previously been applied to 

oncogenes, they successfully inhibited the 

protein by chemically binding, or tethering, 

small molecules to the part of the protein 

that was altered by mutation. Additional 

research showed, however, that these small 

molecules bound to what was thought to be 

an inactive form of the protein. Before this 

finding, it had been universally accepted 

that mutant RAS proteins were locked in 

an active state and that successful RAS 

inhibitors would target that active state. 

Not only were these two long-standing 

beliefs overturned by this research, further 

research would show that cancer-causing 

mutants in a RAS-related protein, which 

was supposedly in its inactive state, actually 

exists in the active state.

“Many of the assumptions we’ve made, 

about proteins we’ve studied a lot in 

cancer, are wrong,” Kevan said, “and these 

assumptions are hindering our ability to 

make discoveries.” He believes that findings 

like these underscore the need for more 

basic research. He also said that it is very 

important for NCI to sustain funding for 

cancer drug discovery aimed at high-value 

targets, such as RAS, and even to prioritize 

high-risk, high-reward science. “We don’t 

have enough discoveries on the table to add 

them up in different ways to construct the 

next major drug,” he said. “We need more 

discoveries.”

16

Find videos at plan.cancer.gov
17

Learning How Cancer Spreads and How to Stop It

In the future, clinicians will be able to accurately predict whether a given cancer will 

spread (metastasize) to another part of the body. Treatments tailored to the individual 

patient to prevent or block metastasis will also be possible. Before that day can come, 

however, we must acquire a deeper understanding of how cancer spreads and thrives in 

new locations. Although great progress has been made over the last two decades in the 

treatment of cancer, metastasis remains cancer’s most lethal aspect.

The “seed and soil hypothesis” of cancer metastasis was proposed more than 125 years 

ago. In this hypothesis, successful metastasis occurs only when distant organs and 

tissues (the “soil”) are suitably hospitable to cancer cells (the “seeds”) to allow them to 

survive and grow into new tumors. Although this basic premise still holds, metastasis is 

now known to be more complex than just a seed finding suitable soil. The type of cancer, 

the ability of the spreading cells to survive in the circulatory system, and the organ or 

tissue to which they spread all influence how the metastatic process unfolds.

Another important factor is when cancer cells spread. For many years, it was thought that 

metastasis occurred late in tumor development, but recent evidence indicates that cancer 

cells can spread throughout the body before the development of a palpable tumor. For 

example, using a mouse model of breast cancer, NCI-funded researchers were able to 

show that cancer cells can spread from a tumor even before the tumor is large enough 

to be detected. In addition, the cells that spread early were more likely to give rise to 

metastatic tumors than cells that spread later in tumor development.

These findings have implications for the early detection and treatment of metastatic 

tumors. However, many unanswered questions remain, and additional research is 

needed to make progress for patients.

To prevent or significantly delay the lethal outcome of metastatic cancer

THE VISION

THE APPROACH

• Support research to increase our understanding of the metastatic process, including 

the timing of events that lead to metastatic disease and where in the body 

metastasis occurs

• Develop cellular and animal models that faithfully represent the metastatic process 

in humans 

Research Priorities

NCI supports research that investigates all aspects of the metastatic process, from how 

tumor cells metastasize to why certain cancer types colonize some organs and not others.
18

Understanding Cancer

Understand How Distant Tissues Are Conditioned for Metastatic Colonization

The local environment in an organ or tissue where a metastatic tumor will eventually 

grow is not a passive player in the process of metastasis. NCI-funded researchers 

have shown that this environment must first be conditioned to create a hospitable 

neighborhood—termed a premetastatic niche—before the spreading tumor cells arrive.

Subsequent discoveries have shown that tumors play an active role in creating this 

niche by, among other things, sending out tiny messengers called exosomes. Tumor cell 

exosomes contain cellular components, such as DNA and proteins, wrapped up in a piece 

of the tumor cell’s outer membrane. They transport their contents through the body’s 

circulatory system to help condition distant locations for metastatic colonization. NCIfunded researchers are exploring the use of exosomes and other tumor-secreted vesicles 

as biomarkers and potential therapeutic targets for predicting and preventing metastatic 

disease. (Read about one of these researchers, David Lyden, M.D., Ph.D., of Weill Cornell 

Medical College, on page 20.)

Another area of investigation is understanding why specific cancers preferentially 

metastasize to certain organs or tissues but not to others. For example, breast 

and prostate cancers often metastasize to the bones, and gastrointestinal cancers 

frequently metastasize to the lungs and liver. The factors underlying this tissue-specific 

predisposition for metastasis are largely unknown and are being studied by the cancer 

research community. Identifying these factors may reveal strategies to limit 

metastatic disease.

Investigate When Metastasis Occurs

Cancer cells that have spread from a tumor to a distant location may grow to form a new 

tumor, die, or become dormant. Some cancer cells can remain dormant for 5, 10, or even 

20 years before they begin to divide again and form a metastatic tumor. Advances in 

technology have made it possible to study this phenomenon, called metastatic dormancy, 

by tracking single cells in animal models and characterizing them at the molecular 

level. In one example, NCI-funded researchers identified a specific gene signature as a 

potential biomarker of dormancy in single disseminated prostate cancer cells isolated 

from the bone marrow of patients. Whether this biomarker can be used to monitor early 

recurrence in prostate cancer patients is being explored.

Develop Models to Understand Metastasis

Achieving a better understanding of cancer metastasis will require new approaches and 

models to study the process and how it affects patients. Some NCI-supported programs 

and initiatives designed to address these needs include the following:

• The Oncology Models Forum, which is a platform for scientists to share information 

about animal models, including information about generating, validating, and 

credentialing new mouse models. In addition, patient-derived xenograft (PDX) 

mouse models have generated excitement due to their ability to better predict 

responses to treatment, and, as they are refined, they may prove useful in 

metastasis research.
19

• The Provocative Questions Initiative, through which new approaches to studying 

metastasis are being developed with NCI support. NCI has funded seven metastasisrelated research projects under this initiative, including one to develop a metastasison-a-chip assay. Although this assay is still in the early stages of testing, it has the 

potential to be used for studying how metastatic cells migrate and, ultimately, for 

testing drugs to inhibit the metastatic process.

• The Cancer Systems Biology Consortium, which integrates biology, mathematics, 

computer modeling, and engineering technology to further advance studies of the 

complexity of cancer. One of the nine academic centers in the consortium focuses 

specifically on cancer metastasis, and other consortia members study various 

aspects of metastasis.

• NCI supports fundamental research in cancer metastasis to develop ways to prevent or block metastasis and better 

treat patients with metastatic disease. 

• This research includes studies to increase our understanding of how tumor cells colonize distant organs or tissues, 

why they preferentially spread to certain sites, and what controls the timing of metastatic spread.

• NCI also supports the development of models that better represent the metastatic process in humans.

KEY TAKEAWAYS
20

Understanding Cance r

DAVID LYDEN, M.D., PH.D.

Stavros S. Niarchos Chair, Weill 

Cornell Medical College

Pediatric Neuro-Oncologist, Memorial 

Sloan Kettering Cancer Center

Metastasis causes about 90% of deaths 

from cancer. Understanding how 

cancer spreads throughout the body could 

reveal new opportunities to curtail tumor 

growth and help prolong the lives of cancer 

patients. Pediatric neuro-oncologist and 

researcher David Lyden is an NCI-funded 

scientist who has worked arduously for 

nearly two decades to uncover the steps of 

cancer cell metastasis.

David’s research focuses on exosomes, 

tiny sac-like structures, or vesicles, that 

are secreted by cells and circulate in the 

blood. Until recently, researchers had 

largely ignored exosomes and believed 

that tumor cells alone initiate metastasis at 

distant sites. However, David and his team 

discovered that, long before cancer cells 

arrive at a distant site, tumor exosomes 

help create a nurturing, or conditioned, 

environment for metastatic tumor 

growth. Through this and other work, they 

demonstrated that a primary tumor actively 

prepares so-called premetastatic niches in 

the body.

An unanswered question in metastasis 

research is why certain cancers 

preferentially metastasize to specific sites. 

For example, lung cancers often spread to 

the brain, and prostate cancers regularly 

spread to the bones. Expanding on their 

previous findings, David’s team made a 

discovery that sheds light on these patterns. 

“We saw that integrins, specific proteins on 

the surface of exosomes, direct where the 

exosomes will travel in the body,” he said. 

“We think of them as a molecular zip code.”

For example, one exosome might have 

integrins on its surface that bind to 

specific cells in the liver, thereby mediating 

metastasis to the liver, whereas another 

exosome might have integrins on its 

surface that bind to cells in the lungs, 

thus facilitating lung metastasis. Once the 

SHINING A SPOTLIGHT ON THE EXOSOME

exosomes have reached their destination, 

they initiate local changes that help support 

the growth of future tumors.

This pioneering work—discovering the 

premetastatic niche and demonstrating 

the critical role of tumor exosomes—has 

ignited a new field of research. The number 

of scientists studying tumor exosomes 

has swelled from several dozen in 2012 to 

more than a thousand in 2017. They are 

increasing our understanding of exosome 

biology and hope to use this information to 

develop new ways to detect and 

treat cancer.

David is very passionate about the future 

of exosome research and is adamant that 

the goal of biological studies should be to 

help patients. “This research could help 

physicians identify patients whose tumors 

are not likely to metastasize, and thus help 

them avoid unnecessary treatment.” He 

thinks it could be possible to identify sites 

of future metastasis by tagging exosomes 

from a patient’s tumor and following them 

with imaging technologies. Furthermore, 

he wonders if blocking tumor exosome 

production may lead to better patient 

outcomes and fewer deaths due 

to metastasis.

PREVENTING 

CANCER
23

Cancer prevention has the potential, in the long run, to save even more lives than 

treatment. With improved prevention, fewer people would face a diagnosis of 

cancer and the physical, financial, social, and psychological harms of the disease 

and its treatment.

NCI’s support of cancer prevention research is particularly critical because the private 

sector is generally not incentivized to make prevention a priority due to the many 

economic, logistical, and scientific challenges that must be overcome. For example, 

most cancers are rare diseases that develop slowly over many years, or even decades. 

Therefore, clinical trials testing the effectiveness of new cancer prevention methods 

require very large numbers of patients and years to conduct.

Although new cancer prevention interventions are greatly needed, full implementation 

of existing evidence-based approaches would greatly reduce the burden of cancer in the 

United States. Research suggests that more than half of all cancer deaths that occur in 

this country each year could be prevented if people quit smoking, drank only moderate 

amounts of alcohol, maintained a healthy body weight, exercised regularly, and received 

recommended cancer screenings and vaccinations.

Current NCI-supported cancer prevention efforts focus on:

• Reducing exposure to cancer-causing agents in the environment, such as tobacco 

smoke, ultraviolet radiation, asbestos, arsenic, and radon gas. 

• Cancer screening tests, such as the Pap smear for cervical cancer and colonoscopy 

for colorectal cancer, which can detect precancerous growths that can be removed 

or destroyed before they progress to cancer. 

• Vaccinations against cancer-causing viruses, such as the hepatitis B virus and highrisk types of human papillomavirus, to prevent persistent infections that lead to the 

development of cancer. About 10% of all cancers are caused by viruses.

An emerging area of opportunity is the development of vaccines to prevent not only the 

cancers that are caused by viruses but also cancers that are not caused by viruses.

Developing Vaccines to Prevent Cancers Not Caused 

by Viruses

We now have safe and effective vaccines against several viruses that cause cancer, but 

can vaccines be developed for cancers that are not of viral origin? That is the goal of NCIfunded researchers who are aiming to use the power of the immune system to prevent 

cancers that are not caused by viruses.

Vaccines are excellent noninvasive, immune-based interventions to prevent cancer. They 

usually have fewer side effects than chemoprevention agents, such as tamoxifen for 

breast cancer prevention, and do not require regular use over many years. In addition, 

the immune system has a memory. This means that vaccination will produce a reservoir 
24

Preventing Cancer

of immune cells that remember a threat to the body and can spring into action if that 

threat is encountered again.

For many years, researchers have been trying to make vaccines to treat patients with 

cancer. Now, they think it may be possible to make vaccines that will prevent certain 

cancers from occurring at all or prevent already treated cancers from recurring.

THE VISION

To develop safe and effective vaccines that prevent cancers not caused by 

infectious agents

THE APPROACH

• Support research to identify, characterize, and test candidate antigens for 

vaccine development

• Enable the development of cancer prevention vaccines through preclinical and 

clinical research

Research Priorities

To advance cancer prevention, NCI supports a range of basic, translational, and clinical 

research necessary for vaccine development.

Support Research to Identify and Characterize Candidate Tumor Antigens

NCI supports research to identify and characterize tumor antigens, which are parts of 

proteins on cancer cells that can trigger an immune response. Tumor antigens that 

trigger the strongest immune responses may become part of vaccine formulations for 

cancer prevention and treatment.

In addition to supporting investigator-initiated research in this area, NCI is launching 

an effort called the Pre-Cancer Atlas (PCA), in which large numbers of precancerous 

growths and early cancers will be systematically collected, catalogued, and analyzed 

comprehensively to understand how different types of cancer arise and progress. The 

creation of this atlas, which will include imaging, genomic, proteomic, and other types of 

data, will be accelerated greatly by the Cancer MoonshotSM. Characterizing the changes 

that occur in the cells of precancerous growths and early cancers should enable the 

identification of potential targets for early intervention, including the development 

of vaccines. (Learn more about PCA on page 32.)

Facilitate the Development of Cancer Prevention Vaccines

NCI programs that support vaccine development include:

• NCI’s PREVENT Cancer Preclinical Drug Development Program, which supports 

early- and late-phase preclinical drug development needs that are not being 

adequately addressed by the private sector. This program is currently supporting 
25

work on several prevention vaccines, including one to prevent colorectal cancer in 

people with Lynch syndrome, a hereditary condition that increases the risk of colon 

and several other types of cancer. People with Lynch syndrome have a defect in their 

DNA repair machinery that results in recurrent mutations at specific protein-coding 

locations in the genome. The mutant proteins stemming from these mutations are 

being investigated as targets for vaccine development.

• NCI’s Phase 0/I/II Cancer Prevention Clinical Trials Program, which supports 

early clinical development of promising prevention agents. To date, 22 trials have 

been supported. One of these trials is a randomized phase II clinical trial of a 

vaccine targeting the tumor antigen MUC1 to prevent colorectal cancer. Abnormally 

modified MUC1 protein is produced by the cells of advanced adenomas, which are 

precancerous polyps in the colon. (Learn more about NCI-supported research on 

this vaccine in the story about Olivera Finn, Ph.D., of the University of Pittsburgh, on 

page 26.)

• NCI supports a wide range of cancer prevention research, including the development of vaccines to prevent cancers 

not caused by viruses.

• One near-term goal of this research is to demonstrate that these vaccines can safely and effectively prevent cancer 

recurrence.

• A longer-term goal is the development of vaccines to prevent multiple types of human cancer.

KEY TAKEAWAYS
26

Prevent ing Cance r

OLIVERA FINN, PH.D.

Distinguished Professor, University of 

Pittsburgh

F or more than two decades, Olivera Finn 

has tirelessly pursued one goal in her 

research: to develop a vaccine to prevent 

cancer. She has had this goal since 1989, 

when her research team discovered the 

first tumor antigen recognized by a type of 

immune cell that can kill cancer cells. That 

antigen—an abnormal version of a protein 

called MUC1—is produced by the cells of 

more than 80% of cancer types, including 

cancers of the breast, pancreas, colon, lung, 

and prostate.

Although she started her research career 

as an organ transplant immunologist, the 

discovery of MUC1 was a pivotal point 

in Olivera’s career trajectory. “Once we 

discovered tumor antigens,” she said, “I 

never looked back.” Olivera received her 

first NCI grant in 1991 and has been funded 

ever since to study the biology of tumor 

antigens and develop them as targets for 

cancer prevention.

Cancer can take many years—even 

decades—to develop. Some cancers 

arise from precursor growths that can be 

detected by current screening methods. 

For example, colorectal polyps called 

advanced adenomas, which can be detected 

by colonoscopy, can progress to colorectal 

cancer. These adenomas can be removed 

surgically, but in many patients, new ones 

continue to develop and some will become 

malignant. Olivera’s lab found that the cells 

of advanced adenomas and the precursors 

of pancreatic, lung, and many other types of 

cancer all produce abnormal MUC1 protein. 

The presence of abnormal MUC1 on 

premalignant growths may make it a good 

target for a vaccine that would prevent their 

progression to cancer or the development 

of new precursors. To test this idea, 

Olivera’s group conducted the first ever 

clinical trial of a cancer prevention vaccine 

based on a tumor antigen in healthy people 

PURSUING A CANCER PREVENTION VACCINE

without cancer who were at increased risk 

of developing the disease.

In the NCI-funded trial, reported in 2013, 

individuals with a history of advanced 

adenomas were given an MUC1 vaccine. 

The vaccine was shown to be safe and to 

elicit a strong immune response and a longlasting immune memory. NCI is currently 

sponsoring a phase II trial testing whether 

the vaccine will prevent the regrowth of 

colorectal polyps.

Looking forward, Olivera envisions, “If you 

are in your 60s and your doctor discovers 

you are at high risk for cancer, the idea 

would be to vaccinate to boost the immune 

system’s ability to keep any abnormal cells 

in check instead of waiting to see if 

cancer develops.”

Olivera says that funding from NCI is 

critical for her research and for cancer 

prevention research in general. Cancer 

prevention research is complex, and 

translating laboratory discoveries into new 

ways to prevent cancer requires sustained 

investments over many years—investments 

that the private sector is often reluctant 

to make. But “building the evidence that 

vaccines are an effective way of controlling 

cancer will go a long way toward getting 

companies interested,” she said.

The field of cancer immunology has 

expanded dramatically and has led to 

immunotherapies for the treatment of 

advanced cancers as well as vaccines 

against some viruses that cause cancer. 

Boosting the immune system to prevent 

cancers that are not caused by viruses may 

now be within reach. “The opportunities are 

amazing,” she added.
27

Preventing Virus-Associated Cancers

More than 2 million cancers worldwide each year are caused by 10 different infectious 

agents. Seven of these agents are viruses, including the human papillomavirus (HPV, of 

which there are 13 high-risk types), the hepatitis B virus (HBV), the hepatitis C virus (HCV), 

and the Epstein-Barr virus (EBV).

The HPV vaccines that are currently available are highly effective in preventing the 

development of high-grade cervical lesions, which are precursors to cervical cancer that 

are caused by persistent infections with high-risk HPV types. Because the same HPV types 

(16 and 18) that cause about 70% of all cervical cancers also cause most cases of vaginal, 

vulvar, anal, penile, and oropharyngeal cancers, immunization may reduce the incidence 

of these cancers as well. 

Despite the ready availability of HPV vaccines in the United States, vaccination rates 

remain low. These low vaccination rates stand in sharp contrast with the vaccination rate 

for another cancer prevention vaccine, the HBV vaccine. HBV is a major cause of liver 

cancer, and vaccination against this virus is nearly universal in this country.

THE VISION

To prevent the ability of viruses to cause cancer through the development and 

widespread application of additional vaccines

THE APPROACH

• Broaden the prevention of HPV-associated cancers

• Develop new vaccines against additional viruses that cause cancer

Research Priorities

Additional NCI-funded research will build on efforts against HPV-associated cancers and 

focus on other cancers that have viral causes.

Broaden the Prevention of HPV-Associated Cancers

NCI efforts against HPV-associated cancers include the following:

• NCI is sponsoring a clinical trial to assess the efficacy of immunization with one 

dose of HPV vaccine. This research builds on previous NCI-led research that showed 

that two doses of HPV vaccine were as effective as three doses, a finding that 

changed national vaccine guidelines for younger adolescents. The finding that 

two doses is sufficient for this group is important because administering fewer 

doses is logistically simpler and more cost effective, which is especially important 

in resource-poor areas. One dose would further reduce costs and improve vaccine 

uptake, thereby having a greater impact on preventing cervical and, possibly, several 

other types of cancer.

29

• HPV vaccines work best when given before a person is exposed to the virus. For 

women already exposed and at risk of cervical cancer, NCI-supported researchers 

are trying to develop vaccines against virus antigens associated with HPV-induced 

cancers. These antigens include the HPV proteins E6 and E7. Vaccines targeting 

these antigens may prevent high-risk precancerous growths from progressing to 

cervical cancer.

Develop New Prevention Methods against Additional Cancer-Causing Viruses

The successful production of vaccines against additional viruses that cause cancer will 

have tremendous global impact. For example, Epstein-Barr virus (EBV) infections cause 

an estimated 200,000 new cases of cancer each year worldwide. Vaccines against EBV, 

which causes Burkitt lymphoma, some types of Hodgkin and non-Hodgkin lymphoma, 

and about 10% of gastric (stomach) cancers, are in development. NCI also supports 

research that is essential to understanding how EBV interacts with other risk factors to 

drive cancer development and to find other ways to intervene to prevent 

EBV-associated cancers.

• NCI is supporting research to broaden the use of currently available vaccines against cancer-causing viruses.

• NCI is also supporting research to develop additional vaccines against the currently targeted viruses and other 

cancer-causing viruses. 

• The ultimate goal of this research is to prevent cancer caused by viruses.

KEY TAKEAWAYS
DETECTING & 

DIAGNOSING 

CANCER
31

Early detection is a proven strategy for saving lives from cancer. The early detection 

of cancer greatly increases the chances of successful treatment. Far too often, 

however, cancers are diagnosed at later stages, when curative treatment is no 

longer possible.

The best scenario would be to have the ability to identify precancerous growths that 

are destined to become life-threatening cancers, providing the opportunity for early 

intervention to prevent cancer from developing altogether. Moreover, the ability to 

accurately identify abnormal growths that will not progress to potentially fatal cancers 

would spare patients the physical and financial harms of unnecessary treatment and the 

psychological harms of a cancer diagnosis.

Areas of opportunity include developing new approaches, including liquid biopsies and 

other less-invasive methods, for the early detection of precancers and early cancers. 

These approaches have the potential to increase the number of cancers for which we 

have clinically effective screening programs as well as improve the technologies currently 

used to screen for cancer.

Improving Early Detection to Reduce the Burden of 

Cancer 

Reliably detecting cancer at the earliest possible stage, regardless of where it occurs in 

the body, and accurately identifying people who are at increased risk of cancer are highpriority goals for NCI.

To accurately and reliably detect precancerous growths and early cancers wherever they 

are in the body, thus enabling timely intervention as needed to prevent these abnormal 

growths from becoming life-threatening cancers

THE VISION

THE APPROACH

• Support research to understand how precancerous growths develop and progress (or 

not) to cancer and to identify biomarkers for risk prediction and early detection 

• Improve existing methods for early detection and develop new, noninvasive 

technologies to accurately and reliably detect precancerous growths and early cancers 

Research Priorities

More research is needed to understand how precancerous growths progress to cancer 

and how to translate this knowledge into new and improved technologies for early

cancer detection.
Find videos at plan.cancer.gov

32

Detecting & Diagnosing Cance r

Understand How Precancers Progress to Cancer

NCI supports studies to understand the molecular events that occur during the transition 

from precancerous growths to malignant tumors. This research will lead to new methods 

to detect cancer early, enable better treatment decisions, and improve cancer prevention. 

To address these goals, specific NCI programs include:

• NCI’s Consortium for Molecular and Cellular Characterization of ScreenDetected Lesions, which supports multidisciplinary research at 15 different 

institutions across the country on the molecular and cellular features of cancerous 

and precancerous tumors that have been detected by a cancer screening test. This 

research, which was initiated in 2015, will provide information to help distinguish 

screen-detected tumors that are indolent (nongrowing or slow-growing) from those 

that are aggressive and, therefore, need immediate treatment. The ultimate goal of 

this research is to help doctors and patients decide whether treatment is warranted 

or whether regular monitoring, with the possibility of later treatment, 

is sufficient.

• NCI is also launching a Pre-Cancer Atlas (PCA) program to systematically collect, 

catalogue, and analyze large numbers of precancerous growths and early cancers 

to understand how different types of cancer arise and progress. This effort will 

be greatly accelerated by the Cancer MoonshotSM. Information collected through 

the PCA program will enable the development of more sensitive early detection 

methods. In addition, PCA research will advance cancer prevention efforts. (Learn 

more about how the PCA will aid prevention research on page 24.)

• NCI’s Early Detection Research Network (EDRN) brings together scientists 

from more than 30 different institutions and organizations across the country to 

accelerate the identification and clinical validation of biomarkers of cancer at its 

earliest stages and to evaluate new methods of testing for cancer risk and early 

cancers. EDRN-supported research has led to Food and Drug Administration 

approval of a urine-based test for the detection of prostate cancer and a molecular 

test for the early detection of lung cancer. (Read more about the lung cancer test 

developed by Avrum Spira, M.D., M.Sc., of Boston University, on page 36.)

Improve Current Detection Methods and Develop New Technologies

Our increased understanding of cancer and advanced technological capabilities are 

amplifying opportunities for noninvasive early detection. The development of the liquid 

biopsy and new or improved imaging methods are examples.

• Liquid biopsy: Imagine if a simple blood draw in a doctor’s office could be used to 

detect, stage, or monitor cancer. Perhaps one of the most rapidly evolving areas 

in cancer research is identifying and validating tumor biomarkers in blood, urine, 

sputum, or other bodily fluids. Investigators, including many supported by NCI, 

have discovered that cancer cells and molecules released from them (such as DNA 

and RNA) can be detected in these fluids. The process of collecting samples of 

bodily fluids, known as a liquid biopsy, is simple, minimally invasive, and can be 

repeated on a regular basis. This approach stands in stark contrast with standard 

Find videos at plan.cancer.gov

34

Detecting & Diagnos ing Cance r

biopsy procedures, in which a tumor is sampled directly, often with surgery. 

However, before this new approach can become broadly useful for early cancer 

detection, much more work needs to be done to develop standardized methods 

to maximize the sensitivity (true-positive rate), specificity (true-negative rate), and 

reproducibility of biomarker identification in specimens of bodily fluids. This effort 

will require improvements in both detection technologies and methods, in addition 

to identifying the most appropriate biomarkers in these fluids. To address these 

challenges, NCI is establishing a Precompetitive Collaboration on Liquid Biopsy 

for Early Cancer Assessment to facilitate public–private partnerships to advance 

this technology for early detection.

• Cancer imaging: Biomedical imaging is important in cancer screening, diagnosis, 

staging, treatment, and the monitoring of disease response or recurrence. Many 

advances in cancer imaging have been made in recent decades, but more work 

remains to improve the sensitivity, specificity, and breadth of available imaging 

techniques. To expedite developments in this area, NCI is creating a Consortium for 

Imaging and Biomarkers, which will foster multidisciplinary collaborative research. 

NCI also sponsors clinical trials of new imaging methods. For example, in 2017, NCI 

launched the Tomosynthesis Mammography Imaging Screening Trial (TMIST)

to compare the effectiveness of 3D digital mammography (breast tomosynthesis) 

and standard 2D digital mammography in detecting breast cancer and reducing the 

incidence of advanced tumors diagnosed.
35

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

• Molecular analysis technologies: There are a variety of other approaches that 

can be used to study precancerous growths and early cancers and to detect 

biomarkers of these lesions. Optimizing the utility of these approaches involves the 

development of improved analytical methodologies and tools. NCI’s Innovative 

Molecular Analysis Technologies program has catalyzed and fostered the earlystage development of highly innovative analytical technologies and tools for 

nearly 20 years, and it continues to support the development of next-generation 

technologies that have the potential to revolutionize the way that precancerous 

growths and early cancers can be studied.

• NCI is committed to identifying and validating biomarkers in liquid biopsy specimens that will allow cancers to be 

detected at the earliest possible stage, when treatment is likely to be most effective and patients have the greatest 

prospects for long-term survival.

• NCI supports the development of new and improved technologies for the noninvasive detection of precancerous 

growths and early cancers.

• NCI supports additional research to improve our understanding of how precancerous growths transition to cancer, 

which will increase opportunities for early detection and cancer prevention.

KEY TAKEAWAYS
36

Detecting & Diagnosing Cancer

AVRUM SPIRA, M.D., M.SC.

Director, Boston University-Boston 

Medical Center Cancer Center

BRUSHING THE AIRWAY TO DETECT LUNG CANCER EARLIER

More people die from lung cancer firsthand in his pulmonary practice, 

than from any other cancer type. Avrum Spira, a physician, researcher, 

In 2017 alone, the estimated number and entrepreneur at Boston University, 

of lung cancer deaths in the United was determined to change that. With 

States will exceed 155,000. Tobacco NCI funding, he is transforming the 

smoking is the prime culprit underlying paradigm of early lung cancer detection 

the development of most lung cancers. and screening.

Sadly, most people are diagnosed with 

late-stage disease that has spread to Avrum’s approach makes use of the 

other parts of the body and is difficult fact that tobacco smoke wreaks havoc 

to treat. on the cells that line the upper airway 

and the lungs, causing damage to their 

Low-dose computed tomography (CT) DNA that can eventually lead to cancer. 

screening can be used to detect lung Drawing on previous ideas about how 

cancer at earlier stages, but false- the toxins in cigarette smoke damage 

positive results, suggesting cancer is a much larger “field” of tissue than the 

present when it is not, are common. precise spot where a malignant tumor 

False-positive results mean that will eventually grow, he reasoned that 

many people who have benign lung it might be possible to test samples 

nodules must undergo invasive and of upper airway tissue for signs of 

painful follow-up tests to see if they genomic damage that are associated 

have cancer. Having experienced the with lung cancer deep within the lung. 

limitations of low-dose CT screening 
4337

To determine whether cells in the 

upper airway, which are much easier 

to sample than cells in a lung nodule 

or tumor, can provide a sign that a 

person has cancer, he piggybacked 

on a minimally invasive endoscopic 

procedure called bronchoscopy. 

This procedure is often used as an 

initial diagnostic test for smokers and 

former smokers who have lesions 

in their lungs that are suspicious for 

cancer. As a stand-alone test, however, 

bronchoscopy misses 40%–50% of 

lung cancers because many nodules 

and tumors are beyond the reach of a 

bronchoscope.

To collect cells from the upper airway 

for analysis, Avrum and his team used 

a bronchoscope equipped with a brush. 

The collected cells were then analyzed 

for molecular changes associated 

with lung cancer. With this approach, 

they identified a characteristic set of 

genomic changes in cells from the 

upper airways of patients with lung 

cancer.

In 2007, Avrum started a company 

that conducted two clinical trials of 

this “bronchial genomic classifier” in 

patients who had not been diagnosed 

with lung cancer from 28 medical 

centers—26 in the United States, one 

in Canada, and one in Europe. The 

trials, which were supported by funding 

from NCI’s Small Business Innovation 

Research (SBIR) program and venture 

capital, were completed in 2014 and 

validated that this test could determine 

the likelihood that lung nodules were 

either benign or malignant.

The company was acquired the 

following year by Veracyte, a publicly 

traded genomic diagnostics company, 

which launched the test commercially 

as Percepta®. In 2017, Medicare began 

covering Percepta® as a diagnostic tool 

to expand the use of bronchoscopy in 

detecting lung cancer.

“It’s gratifying to see something that 

started at the bench make it all the 

way to a patient,” Avrum reflected, 

“but it was a long journey—more 

than 10 years.” Acknowledging NCI’s 

involvement both in the basic research 

and commercialization, he said, 

“Percepta® is now a product because 

of NCI’s support.” Striving to develop 

even better technology, he has found, 

with funding from NCI’s Early Detection 

Research Network, that some of the 

same molecular damage seen in the 

upper airway is also present in the 

nose, which would enable even easier 

and less-invasive testing.
TREATING 

CANCER
39

NCI’s commitment to developing new treatments for cancer patients spans basic 

research to discover the mechanisms of cancer, preclinical research to investigate 

the anticancer effects of therapies that target these mechanisms, and clinical 

research to test new therapies in patients. Despite recent advances in targeted therapy 

and immunotherapy, more needs to be done to substantially improve the outlook 

for both adults and children with cancer. Three areas for further investment include 

developing combination therapies, biomarker-guided immunotherapies, and precision 

medicines that target specific abnormalities in a patient’s cancer.

Combining Therapies to Improve Outcomes

Combination therapies have proven to be vitally important in the successful treatment 

of patients with many types of cancer. Combining treatments that have different 

mechanisms of action can kill more cancer cells and reduce the chance that drug 

resistance will emerge. The overall goal is to improve a patient’s response to therapy 

without substantially increasing toxicity.

In recent years, the identification of new combination therapies has accelerated, 

with hundreds of clinical trials testing combinations that include chemotherapy 

drugs, radiation therapy, hormonal therapies, molecularly targeted therapies, and 

immunotherapies. However, a more systematic approach is needed to identify the most 

promising combinations among the many thousands of possibilities, advance them to 

clinical trials, and make them available to patients who will benefit from them.

NCI plays an important role in supporting the research needed to develop combination 

therapy approaches. In addition, NCI brings different institutions and organizations 

together to advance this area of research. Examples of Food and Drug Administration 

(FDA)-approved drug combinations that have been studied in NCI-sponsored clinical trials 

are docetaxel (Taxotere®), doxorubicin, and cyclophosphamide for breast cancer and 

oxaliplatin (Eloxatin®), 5-fluorouracil, and leucovorin (Wellcovorin®) for colorectal cancer.

To identify the combination therapies that will be most effective for each patient

THE VISION

THE APPROACH

• Support research to identify therapies that, when combined, will work better than they 

would alone

• Systematically evaluate treatment combinations in preclinical studies

• Evaluate the most promising treatment combinations in clinical trials

Research Priorities

NCI advances combination therapies for cancer by supporting preclinical research and 

testing promising combinations in clinical trials.
40

Treating Cancer

Support Basic and Preclinical Research to Identify Combination Therapies

Research should guide the selection of candidate combination treatments. This research 

can provide deeper insights into the mechanism(s) of action of individual treatments, 

how different treatments might work together, the potential side effects that may occur 

when treatments are combined, and how new combinations might be given to patients 

(doses and schedule).

NCI efforts include several resources for researchers:

• To aid in the systematic development of combination therapies, NCI’s 

Developmental Therapeutics Program created the NCI ALMANAC, a public resource 

that contains data on more than 5,000 pairs of FDA-approved drugs that were 

screened at different doses against 60 human cancer cell lines (the NCI-60 Human 

Tumor Cell Lines Screen). In one study, NCI researchers tested two drug pairs in 

the NCI ALMANAC that exhibited potent cell-killing activity. Nilotinib (Tasigna®) 

plus paclitaxel (Taxol®) and bortezomib (Velcade®) plus clofarabine (Clolar®) had 

antitumor activity in several mouse models of human cancer. The results of these 

studies were convincing enough that both combinations are being tested in earlyphase clinical trials.

• Models of human cancer help researchers screen drug combinations for 

effectiveness and study ways to overcome the problem of drug resistance. NCI 

facilitates the development of new models of human cancer, including new tumor 

cell lines and mice bearing patient-derived tumor grafts (known as patient-derived 

xenografts, or PDXs). Some models are available upon request to researchers in the 

United States through the NCI Patient-Derived Models Repository.

Facilitate Clinical Trials of Promising Treatment Combinations

NCI leads several initiatives to investigate promising combination therapies in clinical 

trials, including funding for investigator-initiated trials and resources for researchers.

• NCI has funded more combination therapy studies than any other 

organization. Stories about several of these trials are highlighted in this section, 

including the story of trial participant and ovarian cancer survivor Betsy Brauser 

of Florida (page 42); Valerie Winston of Maryland, who participated in a trial for 

high-risk smoldering myeloma (page 43); and a research team at the University of 

Pennsylvania, who combined radiation therapy with immune checkpoint blockade 

(page 44).

• To facilitate testing of new drug combinations by academic investigators, 

NCI launched the NCI Formulary in 2017. The formulary is a public–private 

partnership between NCI and pharmaceutical and biotechnology companies that 

gives investigators at NCI-Designated Cancer Centers rapid access to agents or 

combinations of agents, from multiple pharmaceutical companies, for preclinical 

testing and clinical trials. The formulary is designed to drastically shorten the 

amount of time needed to obtain treatments from more than one company.
41

• A major activity of NCI’s Cancer Therapy Evaluation Program is oversight of the 

National Clinical Trials Network (NCTN), which can facilitate combination therapy 

trials. NCTN is one of the largest publicly funded cancer trials organizations in 

the world and provides the infrastructure and streamlined mechanisms to plan 

and conduct cancer clinical trials efficiently throughout the United States. NCTN 

facilitates proposal submission, timely review by the collaborating pharmaceutical 

companies, agent distribution, serious adverse event reporting, and clinical 

data reporting, while providing a coordination mechanism between the clinical 

investigators and the pharmaceutical company collaborators.

• NCI is committed to developing new combination therapies that will extend the lives of more cancer patients.

• NCI supports the development of new models of human cancer, including in racial/ethnic populations, to advance 

the testing of combination therapies and find ways to overcome the problem of drug resistance.

• NCI is uniquely positioned to bring together different institutions, organizations, and companies to advance this area 

of research.

KEY TAKEAWAYS
42

Treating Cancer

BETSY BRAUSER

Ovarian Cancer Survivor

Florida

Betsy Brauser was diagnosed with stage IIC ovarian cancer in 2009. She 

underwent standard platinum-based 

chemotherapy, and her doctors gave her 

an all-clear. But a year later, scans revealed 

her cancer had returned. So, she found a 

phase I clinical trial for patients with ovarian 

cancer at the NCI-Designated Dana-Farber/

Harvard Cancer Center in Massachusetts.

Ovarian cancer is the fifth leading cause of 

cancer death among women in the United 

States. “Approximately 70% of the women 

diagnosed with ovarian cancer will die from 

the disease,” explained Joyce Liu, M.D., a 

principal investigator of the trial. “It’s critical 

that we find more effective and better 

tolerated treatments to help women live 

better and live longer,” she said.

So, Joyce and her colleagues at DanaFarber designed a trial combining the 

Food and Drug Administration-approved 

drug olaparib (LynparzaTM) with the 

investigational drug cediranib. Olaparib 

inhibits an enzyme called PARP, and 

cediranbib inhibits the growth of blood 

vessels that tumors need to grow larger 

than about 1 mm in size.

Joyce received support from NCI in 2008, 

when she began developing the phase I 

trial, her first investigator-initiated trial 

as an early-career researcher. She drew 

on several NCI-funded preclinical studies 

that indicated these drugs might work 

much better together than either worked 

alone. “It’s an exciting possibility that we 

might make a tumor more vulnerable 

to a drug by adding a different class of 

drugs,” she reflected. “That’s the power of 

combination—having a true 

synergistic effect.”

Betsy enrolled in Joyce’s trial and spent 

the next several years commuting to 

COMBINING DRUGS TO TREAT OVARIAN CANCER

Boston for treatment. Scans taken at 3- to 

4-month intervals showed her tumors were 

shrinking, and, eventually, her doctors 

reported that they found no evidence of 

disease. Betsy and her family were elated.

Betsy continues to receive follow-up checks 

on the trial, which has moved successfully 

from a phase I and then phase II trial into an 

NCI-sponsored phase III trial to determine 

whether the combination regimen is more 

effective than olaparib or chemotherapy 

alone. She hopes that scientists continue 

conducting research and developing drugs 

to help other patients with ovarian cancer. 

Joyce agrees: “We need to understand what 

drives ovarian cancer at a biological level 

and find new ways to overcome resistance 

to platinum-based drugs. Combinations of 

therapies that build on our understanding 

of the various types of ovarian cancer will 

go a long way toward helping doctors better 

treat their patients.”
43

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

STOPPING MULTIPLE MYELOMA IN ITS TRACKS

Valerie Winston is thankful that she 

went to her doctor for a routine 

physical examination in 2009. The results of 

standard tests indicated that she was at risk 

for multiple myeloma. Thanks to a clinical 

trial testing a combination of therapies for 

individuals like Valerie, she never had to 

experience cancer’s full impact.

Multiple myeloma will be diagnosed in 

approximately 30,280 Americans in 2017, 

and an estimated 12,590 of them will die 

from it. Multiple myeloma is a cancer of 

plasma cells—cells in the immune system 

that help the body fight infection. Abnormal 

plasma cells make proteins called M 

proteins, which are abnormal antibodies 

that build up in the bone marrow and can 

damage the body. An M protein is what 

Valerie’s doctors detected.

Because Valerie had low levels of the M 

protein and no other symptoms of cancer, 

she was diagnosed with a condition called 

monoclonal gammopathy of undetermined 

significance (MGUS). MGUS is not cancer, 

but, in some cases, MGUS can progress to 

multiple myeloma. Valerie’s initial elation 

that the condition had been caught early 

dimmed when her doctors told her that 

they would need to “watch and wait” to see 

if cancer developed before they could treat 

her. 

Valerie was monitored, and, eventually, she 

progressed to a disease called smoldering 

myeloma, which is a stage between MGUS 

and multiple myeloma where myeloma cells 

are present but not causing bone or organ 

damage. Now, she was deemed at high 

risk for progression to full-blown multiple 

myeloma.

Because more than 90% of patients with 

high-risk smoldering myeloma develop 

multiple myeloma within 2–5 years, 

researchers are working to intervene in this 

process. One way is by testing drugs against 

high-risk smoldering myeloma that have 

been successful against multiple myeloma. 

Impatient to do something beyond 

“watching and waiting,” Valerie found a 

clinical trial at NCI. “I went into the trial with 

the attitude that, if it doesn’t help me, then 

my participation will help someone else in 

the future,” she said.

The trial Valerie participated in tested 

lenalidomide (Revlimid®), dexamethasone, 

and carfilzomib (Kyprolis®), three drugs 

that are already approved by the Food 

and Drug Administration to treat multiple 

myeloma. Researchers wanted to see if the 

combination of these drugs would provide 

a safe and effective treatment for patients 

with high-risk smoldering myeloma.

Valerie began showing good results by 

the 3rd month of treatment, and, by the 

9th month, doctors proclaimed she had 

experienced a complete response. In fact, 

all 18 patients in the trial responded to the 

treatment. Although it was a small study, 

these results provide evidence to support 

larger trials in the future that will determine 

more definitively whether the benefits of 

this experimental treatment outweigh the 

harms.

Despite having some side effects from 

treatment, Valerie is grateful to have 

participated in the trial. She is now a 

messenger about the importance of 

research to family, friends, and anyone who 

will listen. “I talk to my relatives and others 

about this,” she said. “We all have a part 

to do. I feel great about being part of this 

progress.”

VALERIE WINSTON

Smoldering Myeloma Survivor 

Maryland
44

ROBERT (BOB) 

VONDERHEIDE, M.D., D.PHIL.

Director, Abramson Cancer Center, 

University of Pennsylvania

ANDY MINN, M.D., PH.D.

Associate Professor of Radiation 

Oncology, University of Pennsylvania

Treat ing Cance r

CHRISTINA TWYMAN-SAINT 

VICTOR, M.D.

Assistant Professor of Medicine, 

University of Pennsylvania

JOINING FORCES AGAINST CANCER

Across-disciplinary team of scientists 

and physicians at the University of 

Pennsylvania is redefining the role of 

one of cancer medicine’s oldest tools 

and blazing a new trail in the treatment 

of patients. Their efforts, led by cancer 

immunologist and oncologist Bob 

Vonderheide and radiation oncologist 

Andy Minn, are demonstrating the 

promise of combining immune 

checkpoint inhibitors and radiation 

therapy. 

Radiation therapy has been used to 

treat patients with cancer since the 

beginning of the 20th century. About 

half of all cancer patients receive some 

type of radiation therapy. It is typically 

used as a local therapy—that is, to treat 

the specific area of the body where a 

tumor is located. However, mounting 

evidence supports the idea that 

local radiation can also have effects 

throughout the body and that these 

effects are mediated by the immune 

system.

In fact, researchers are finding that 

as irradiated cancer cells die, they 

trigger an immune response much 

like vaccines do. Bob, Andy, and their 

colleagues—calling themselves the 

RadVax team (Rad for radiation and 

Vax for vaccine)—are testing the idea 

that the immune response triggered 

by radiation can be improved further 

by the addition of immune checkpoint 

inhibitors, a type of treatment that 

enhances the ability of the immune 

system to kill a tumor. If successful, 

the combination therapy will provide 

additional options for patients with 

metastatic cancer, including patients 

who do not respond to checkpoint 

inhibitors alone.

In 2015, the team reported results from 

the first clinical trial of radiation therapy 

combined with the immune checkpoint 

inhibitor ipilimumab (Yervoy®), which 

targets a protein called CTLA-4. In 

addition to testing the combination in 

patients with metastatic melanoma, 

they also studied it in mouse models 

of melanoma to gain further biological 

insights.

Although responses were observed 

in some of the patients, most did not 

benefit. However, studying both the 

mice and patient samples uncovered a 

resistance mechanism—a way in which 

the melanoma cells avoided being killed 

by the immune system—that likely 

explained the clinical findings. This 

led the team to their current strategy 

of deploying multiple checkpoint 

antibodies along with radiation. The 

triple combination, effective in mice, 

is currently being tested in patients in 

clinical trials.

Bob credits the NCI Cancer Center 

Support Grant (CCSG) to Abramson 

Cancer Center for the team’s success. 

Access to the infrastructure and 

personnel supported by the CCSG 

enabled the researchers to be nimble 

and get the studies off the ground 

quickly. This was a “CCSG in action,” 

said Bob.

The team that accomplished this study 

consisted of 25 researchers from a 
453

variety of scientific disciplines and 

included early-career and established 

investigators. Notably, the study’s first 

author Christina Twyman-Saint Victor 

was completing her research training 

at the time and is now an independent 

investigator with her own laboratory at 

Penn.

Additional clinical trials testing 

combinations of radiation therapy 

and immune checkpoint inhibitors are 

currently being conducted. Still, “there 

are many scientific questions that still 

need to be answered,” said Andy. With 

NCI’s support, the RadVax team aims 

to answer them. For example, more 

needs to be known about how these 

treatments interact at the cellular and 

molecular level to inform how best to 

combine them.

In 2017, NCI awarded Bob and Andy, 

along with Professor of Radiation 

Oncology Amit Maity, M.D., Ph.D., and 

Distinguished Professor of Microbiology 

E. John Wherry, Ph.D., a grant to 

continue this work in four cancer types. 

“Our team has one goal: to improve the 

health of patients,” said Bob. “We are 

using science to do that.”
46

Treating Cancer

Developing Precision Immunotherapies

Immunotherapy is a type of treatment that helps the body’s immune system fight cancer. 

Several kinds of immunotherapy, including immune checkpoint inhibitors, adoptive 

cell transfer, and therapeutic vaccines are either commercially available or in clinical 

development. To date, six immune checkpoint inhibitors have been approved by FDA for 

the treatment of eight types of cancer.

One of the inhibitors has also been approved to treat any solid tumor that has a specific 

genetic feature. This was the first FDA approval of its kind and a major advance for 

precision cancer medicine, in which the molecular characteristics of a tumor are used to 

identify effective therapies. (Read more about this drug approval on page 52.) 

Recent advances in cancer immunotherapy are the result of several decades of basic 

research, much of it supported by NCI, on the function of the immune system and how it 

can be used for the treatment of cancer.

FDA-Approved Immune Checkpoint Inhibitors

Inhibitor Target Cancer Type(s)

Atezolizumab 

(Tecentriq®) PD-L1 Bladder cancer 

Non-small cell lung cancer

Avelumab 

(Bavencio®) PD-L1 Bladder cancer 

Merkel cell carcinoma*

Durvalumab 

(ImfinziTM) PD-L1 Bladder cancer

Ipilimumab 

(Yervoy®) CTLA-4 Melanoma*

Bladder cancer 

Head and neck cancer (squamous cell carcinoma) 

Classical Hodgkin lymphoma 

Nivolumab 

(Opdivo®) PD-1 Melanoma 

Mismatch repair deficient and microsatellite instability-

 high colorectal cancer* 

Non-small cell lung cancer 

Renal cell (kidney) cancer

Bladder cancer 

Head and neck cancer (squamous cell carcinoma) 

Pembrolizumab 

(Keytruda®) PD-1

Classical Hodgkin lymphoma†

Melanoma 

Mismatch repair deficient and microsatellite instability- 

 high solid tumors†

Non-small cell lung cancer

*patients age 12 and older 

†pediatric and adult patients 
47

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Despite the remarkable progress made to date in cancer immunotherapy, most patients 

do not benefit from currently available treatments, and these therapies can be toxic 

to some individuals. Understanding why these treatments are not beneficial for more 

patients is a pressing question for scientists. However, NCI-funded research has led to 

the identification of two biomarkers that can help determine which patients are more 

likely to respond to checkpoint inhibitor therapy: PD-L1 and a genetic feature called 

microsatellite status. Patients whose cancers have these biomarkers are more likely to 

respond to checkpoint inhibition than patients whose cancers do not. (Read about why 

more biomarkers are needed for patients in the story about melanoma survivor T.J. 

Sharpe of Florida on page 50.)

NCI supports a wide range of research, from basic research to clinical trials, to advance 

the field of cancer immunotherapy. Through this work, the benefits of immunotherapy 

will be extended to more patients with cancer.

To develop safe and effective immunotherapy options for all patients with cancer

THE VISION

THE APPROACH

• Advance research on the mechanisms of immunotherapy 

response, resistance, and toxicity

• Support research, infrastructure development, and collaboration 

to discover and validate clinically useful immunotherapy 

biomarkers

Research Priorities

Additional basic research, translational studies, and clinical trials are 

critical for further elucidating the mechanisms of immunotherapy 

response, resistance, and toxicity and for identifying additional 

biomarkers to guide treatment selection.

Advance Research on Mechanisms of Immunotherapy Response, 

Resistance, and Toxicity

The effectiveness of immunotherapy in patients is influenced 

by several factors, including interactions between cancer cells, 

immune cells, and stromal (connective tissue) cells in the tumor 

microenvironment and the characteristics of the cancer cells 

themselves. Research is leading to key discoveries about these 

factors, but more work is needed to increase this knowledge and 

translate it into safer and more-effective immunotherapy options for 

patients. This ongoing research includes studies of:

• The tumor microenvironment: To eradicate cancer cells, 

immune cells (white blood cells) must travel to the site of the 
48

Treat ing Cance r

tumor and infiltrate it. However, some tumors, including pancreatic and prostate 

tumors, can exclude immune cells from their microenvironment, making then 

unresponsive to immunotherapy. These tumors are called “noninflamed” or “cold” 

tumors. In contrast, “inflamed” or “hot” tumors, such as melanoma, contain 

immune cells in the tumor microenvironment and, therefore, tend to respond better 

to immunotherapy. How noninflamed tumors exclude immune cells and whether 

they can be turned into inflamed tumors are major unanswered questions that NCIsupported research is addressing. 

• Immune cells: Although a particular type of white blood cell is directly responsible 

for killing tumor cells, many other types of immune cells are involved in either 

promoting or suppressing immune responses against cancer. Scientists aim to 

better understand how these different cells interact with one another. As an 

example, NCI-funded researchers discovered that breast cancer cells and immune 

cells called macrophages “talk” by secreting factors that support tumor growth 

and invasiveness. The cancer cells secrete a protein called colony stimulating factor 

1 (CSF-1) that stimulates the macrophages to produce a protein called epidermal 

growth factor (EGF). The EGF, in turn, promotes further cancer cell production of 

CSF-1, thereby generating a positive feedback loop.

• Cancer cells: Research funded by NCI and led by Suzanne Topalian, M.D., and her 

colleagues at Johns Hopkins University demonstrated that tumors with high levels 

of the protein PD-L1 tend to respond better to PD-1 inhibitors. PD-L1 binds to the 

PD-1 protein on immune cells, suppressing an immune response. This finding 

and additional research by others led to FDA-approved tests that measure PD-L1 

expression on patients’ tumors—making PD-L1 the first approved biomarker to 

guide the use of cancer immunotherapy. In another area of research, NCI-funded 

scientists have identified specific gene mutations and patterns of gene expression in 

certain cancer types that indicate responsiveness or resistance to PD-1 inhibitors.

Support Collaboration and Data Sharing to Discover and Validate 

Immunotherapy Biomarkers

Sharing samples and data through research and clinical trial networks will help advance 

research in cancer immunotherapy. There are several NCI-supported efforts that will help 

facilitate this sharing.

• The Cancer Immunotherapy Trials Network (CITN), which was established in 

2010 to design, facilitate, and conduct early-phase immunotherapy clinical trials 

and support research on patient tumor specimens. The network currently has 30 

participating trial sites and has conducted 10 clinical trials to date. CITN works with 

academic, industry, and nonprofit partners to advance promising immunotherapies 

to the clinic more efficiently and cost effectively. For example, the network led a 

phase II clinical trial that demonstrated the effectiveness of the checkpoint inhibitor 

pembrolizumab in patients with Merkel cell carcinoma, a rare but aggressive form of 

skin cancer.
49

• Other NCI clinical trial networks, including the Experimental Therapeutics 

Clinical Trials Network and the National Clinical Trials Network, which provide 

infrastructure, funding, and sponsorship for immunotherapy and other treatment 

trials. Since 2010, more than 90 phase I to phase III trials have been initiated 

in NCI networks for immunotherapy agents and novel combinations involving 

immunotherapy. Most trials incorporate research on biomarkers and other studies 

to better understand why these therapies work for some patients and not others.

• In 2017, NCI announced the formation of a new network of laboratories that will 

be responsible for the comprehensive molecular analysis of clinical trial specimens 

for biomarkers associated with response to immunotherapy. The Cancer Immune 

Monitoring and Analysis Centers (CIMACs) will conduct correlative studies and 

profiling of tumors and immune cells for NCI-funded early trials of immunotherapy. 

Part of this effort includes the creation of a Cancer Immunologic Data Commons 

(CIDC) to support the bioinformatics needs of the CIMACs. The database created 

by the CIDC will serve as a resource for the identification of novel biomarkers and 

targets for patient selection and treatment, as has been done with NCI’s Genomic 

Data Commons for genomic data.

• As part of the Cancer MoonshotSM, NCI is establishing two networks to accelerate 

the translation of immunotherapy research discoveries to clinical applications 

for adult and pediatric cancers. For adult cancers, the Immuno-Oncology 

Translational Network aims to improve outcomes for patients who are treated 

with immunotherapy and to prevent cancers before they can occur through 

immunoprevention approaches. The Pediatric Immunotherapy Discovery and 

Development Network will identify new targets for immunotherapies, developing 

new pediatric immunotherapy treatment approaches, and defining the biological 

mechanisms by which pediatric tumors evade the immune system.

• NCI supports research to develop safe and effective immunotherapy options for all cancer patients.

• NCI funds research to determine the mechanisms of immunotherapy response, resistance, and toxicity to aid in the 

discovery of biomarkers that will be useful in guiding clinical decision making.

• NCI facilitates sharing samples and data through research and clinical trial networks that advance research in cancer 

immunotherapy.

KEY TAKEAWAYS
50

Treating Cancer

T.J. SHARPE

Melanoma Survivor

Florida

MAKING THE CASE FOR BIOMARKERS

I

n August 2012, just weeks after the 

birth of his second child, 37-yearold T.J. Sharpe walked into his local 

emergency room with a spiking fever 

and did not leave for more than 2 weeks. 

He was blindsided by the diagnosis he 

received: metastatic melanoma. Twelve 

years earlier, a stage IB melanoma had 

been removed from his chest. T.J. had 

been careful about his sun exposure 

ever since. But now, melanoma tumors 

riddled his lungs, liver, spleen, and 

small intestine.

T.J.’s first oncologist recommended 

chemotherapy and expressed doubt 

that he would be alive in 2 years. T.J. 

and his wife, Jen, deciding that was 

not acceptable, sought additional 

medical opinions and, ultimately settled 

on a clinical trial that was testing a 

combination of immunotherapies 

that had not previously been given 

to patients. T.J. did not benefit from 

this trial. “I was the first to try that 

combination, and I was the first to fail it,” 

he said. The regimen was arduous, and 

he experienced many complications.

Despite this setback, he enrolled in 

another trial. “I knew that clinical 

research was far from a guarantee but 

held the promise of hope,” he said. “My 

children, Josie and Tommy, were growing 

up right in front of me, and I was willing 

to endure anything.” Within a matter of 

weeks of receiving his first dose of the 

drug being tested in the new trial—a 

PD-1 checkpoint inhibitor—his tumors 

shrank by half. Five years later, T.J. 

remains cancer free.

Based on the success of this and many 

other clinical trials, the Food and Drug 

Administration (FDA) has approved five 

PD-1/PD-L1 checkpoint inhibitors to treat 
4351

melanoma and other cancers since 

2014.

NCI supported the initial work 

necessary to unleash the immune 

system against cancer with studies of 

ipilimumab (Yervoy®), the first immune 

checkpoint inhibitor to be approved 

by FDA. Ipilimumab blocks an immune 

checkpoint protein called CTLA-4. 

NCI-funded research had shown that 

blocking CTLA-4 improved the ability 

of the immune system to attack cancer 

in animal models. This pioneering 

work formed the basis of ipilimumab’s 

approval for patients with metastatic 

melanoma in 2011 and paved the way 

for future immunotherapies like the 

one that T.J. received.

Long-term follow-up of melanoma 

patients treated with ipilimumab in 

clinical trials have demonstrated that 

approximately 20% of patients were 

still alive 10 years later. Follow-up data 

from trials of approved PD-1 inhibitors 

show that approximately one-third of 

patients were alive at least 5 years after 

treatment with nivolumab (Opdivo®), 

and 40% of patients were alive 3 years 

after treatment with pembrolizumab 

(Keytruda®).

For a disease as deadly as metastatic 

melanoma, this is great progress. Yet, 

this also means that most patients do 

not experience a long-lasting benefit 

from the drugs. “Without further 

research, we will never know why I am 

living and so many others have not 

benefited,” said T.J., reflecting on the 

need for biomarkers to help doctors 

identify the best treatment for each 

cancer patient. Several factors influence 

the effectiveness of immunotherapy 

in patients. NCI is supporting ongoing 

work to identify biomarkers of 

immunotherapy response, resistance, 

and toxicity.

It has been 5 years since T.J.’s diagnosis 

with metastatic melanoma. His 

aspirations for the next 5 years include 

watching his son turn 10. “He was just 

weeks old when my melanoma came 

back. Every birthday for him is a small 

milestone for me, too.” Through this 

journey, T.J. became a blogger and 

advocate aiming to make a difference 

in the lives of other patients. “If, for 

some reason, I am not around in 5 

years, I also hope those years are filled 

with impact so that other patients 

and families have the most valuable 

medicine of all—hope.”
52

Treating Cancer

DEVELOPING THE FIRST PRECISION MEDICINE

I

n May 2017, the Food and Drug 

Administration (FDA) approved the 

first drug to treat tumors based on their 

genetic characteristics, regardless of 

where in the body the cancer originated. 

Until now, drugs have been approved 

based on their cell or tissue of origin, 

such as the breast or the lung. But 

pembrolizumab (Keytruda®) doesn’t 

target the genetic abnormalities of 

cancer cells specifically—it targets the 

immune system. 

How did pembrolizumab become the 

first FDA-approved “tumor-agnostic” 

precision medicine drug? This historic 

accomplishment was enabled by 

more than three decades of NCIfunded research in cancer genetics 

and immunology. The drug is now 

available for patients with late-stage 

solid tumors with a genetic feature 

called microsatellite instability-high 

(MSI-H) or mismatch repair deficiency 

(dMMR). Whereas precision medicine 

has focused largely on developing and 

testing drugs that target the genetic 

abnormalities that drive cancer cell 

growth, this new precision medicine 

approach uses the genetic information 

in tumors as a biomarker, not a target, to 

identify patients who may benefit from 

treatment with pembrolizumab.

When the cells of the body divide, their 

DNA must be copied so each progeny 

cell receives a full complement. This 

process, known as DNA replication, is 

not always perfect and mistakes can be 

made. Normally, however, cells have 

ways of repairing these mistakes. In cells 

with dMMR, genes responsible for a DNA 

repair process known as mismatch repair 

are mutated. This DNA repair defect 

can be inherited (as it is in a condition 

called Lynch syndrome), or the defect 

can happen by chance (sporadically). 

The failure of cells with dMMR to repair 

mistakes made in DNA replication leads 

to the accumulation of hundreds to 
534

thousands of mutations, some of which 

can cause cancer.

Lynch syndrome is named after NCIfunded researcher Henry T. Lynch, 

M.D., who discovered the syndrome in 

the early 1970s by studying affected 

families that demonstrated an 

increased risk of colorectal and several 

other types of cancer. In the 1990s, 

several NCI-funded research teams 

investigating the genetics of hereditary 

colorectal cancer determined that 

mutations in mismatch repair genes 

play a key role in this syndrome. Two 

of these teams were led by Richard 

Kolodner, Ph.D., of the Ludwig 

Institute for Cancer Research, and Bert 

Vogelstein, M.D., of Johns Hopkins 

University.

In addition to hereditary and sporadic 

colorectal cancers, dMMR is associated 

with some cancers of the uterus, ovary, 

prostate, stomach, small intestine, 

biliary tract, and pancreas.

Scientists have found that cancers 

with many mutations, such as lung 

cancer and melanoma, are more 

likely to respond to pembrolizumab 

and other immunotherapy drugs 

than cancers with low numbers of 

mutations. Researchers hypothesized 

that tumors with dMMR—because of 

their high number of mutations—might 

also respond to these drugs, including 

pembrolizumab.

One trial, led by Johns Hopkins 

researcher Dung Thi Le, M.D., was 

funded in part by several NCI grants, 

including a Cancer Center Support 

Grant and a Specialized Program of 

Research Excellence Award. Fortyone patients were enrolled in this 

trial, 32 of whom had colorectal 

cancer. Forty percent of patients with 

dMMR colorectal cancer responded 

to treatment, compared with 0% in 

patients without the defect. 

These results and other data led FDA 

to grant pembrolizumab accelerated 

approval for the treatment of 

dMMR cancers. This approval is 

significant because targeting genetic 

characteristics, rather than where the 

cancer originates in the body, opens 

up new options for patients who 

might otherwise not be considered 

candidates for a drug. Furthermore, this 

example demonstrates that decades 

of NCI-funded research in different 

areas, including cancer genetics and 

immunology, has resulted in a whole 

greater than the sum of its parts for 

patients.
54

Treating Cancer

Developing New Treatments for Children with Cancer

Cancer is the leading cause of death from disease among children and adolescents in 

the United States, with approximately 15,000 new cases and 2,000 deaths among those 

ages 19 and younger each year. Fifty years ago, many childhood cancers were virtually 

incurable. However, NCI’s investments in research have led to effective treatments for 

several types of pediatric cancer, including acute lymphoblastic leukemia (ALL) and 

Hodgkin lymphoma. Today, the 5-year overall survival rate for childhood cancer has 

increased to more than 80%, together with substantial decreases in overall mortality for 

children with cancer.

Nevertheless, progress against all cancers that affect children and adolescents is urgently 

needed, especially against those for which effective treatments do not currently exist, 

such as diffuse intrinsic pontine glioma (DIPG) and malignant rhabdoid tumor.

Treatment regimens for children and adolescents with cancer are often associated with 

substantial short-term toxic side effects. In addition, childhood cancer treatments may 

cause serious health problems for survivors months or years later, including higher 

risks of heart disease, stroke, infertility, and second cancers. More research is needed to 

understand these adverse side effects of treatment and how to prevent or mitigate them.

The rarity of childhood cancers—less than 1% of all cancers diagnosed in the United 

States each year—makes them difficult to study and discourages pharmaceutical 

companies from developing treatments. Consequently, NCI’s leadership and funding are 

critically important for continued progress against childhood cancers.

To have safe and effective therapies for every type of childhood cancer

THE VISION

THE APPROACH

• Support research to develop more-effective, less-toxic treatments for pediatric cancers, 

including molecularly targeted therapies and immunotherapies, and test them in 

clinical trials

• Improve the long-term quality of life of survivors of childhood cancer

• Facilitate greater collaboration among investigators dedicated to childhood cancer 

research

Research Priorities

NCI supports research ranging from the biology of childhood cancer to clinical trials that 

test new cancer treatments in children and adolescents in clinical trials. Two areas of 

focus are molecularly targeted therapies and immunotherapies.

Support the Development of Targeted Therapies for Childhood Cancers

Cancers that arise in children and adolescents often differ from those that arise in 
55

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

adults. For example, they generally have fewer genomic alterations than adult cancers. 

To address this, NCI supports several initiatives to identify the genomic changes that 

drive childhood cancers, develop new treatments to target those changes, and test the 

treatments in precision medicine clinical trials.

• The NCI–Children’s Oncology Group Pediatric Molecular Analysis for Therapy 

Choice (NCI–COG Pediatric MATCH) trial aligns with the Precision Medicine 

Initiative® in oncology. Launched in 2017, this trial will determine whether treating 

cancers based on their molecular abnormalities, rather than the type of cancer, can 

be effective. The trial design was based on the NCI-MATCH trial for adult cancers. 

NCI–COG Pediatric MATCH is open to children and adolescents who have advanced 

solid tumors that have progressed on standard treatment or for which no agreed 

upon standard treatment exists. The trial will enroll patients whose tumors have a 

molecular abnormality that is targeted by one of the approved or investigational 

therapies that are being used in the trial.

• The Therapeutically Applicable Research to Generate Effective Treatments 

(TARGET) initiative has supported a consortium of scientists who are conducting 

comprehensive molecular analyses to identify the genomic changes that drive 

several hard-to-treat childhood cancers. The genomic profiling of pediatric acute 

myeloid leukemia (AML) at initial diagnosis, remission (after treatment), and relapse 

(recurrence) was recently accomplished because of this initiative. This profiling 

confirmed that the genomic features of pediatric AML differ from those in adult AML 

and provided important information to guide future drug development and clinical 

management of the disease.

• The Pediatric Preclinical Testing Consortium is testing cancer drugs in preclinical 

models of pediatric cancers to help prioritize which agents to pursue in human 

clinical trials. The consortium includes NCI and five academic research institutions. 

Albert Einstein College of Medicine is studying models of osteosarcoma; Greehey 

Children’s Cancer Research Institute is studying sarcoma and kidney cancers; Baylor 

College of Medicine is studying brain cancers; Children’s Hospital of Philadelphia 

is studying neuroblastoma; and Australia’s Children’s Cancer Institute is studying 

leukemia.

• Childhood cancers are often driven by so-called fusion oncogenes, which are 

formed when parts of two different genes become joined to one another. To date, 

few treatments have been developed that target the abnormal proteins, or fusion 

oncoproteins, produced by these genes. Developing therapies against pediatric 

fusion oncoproteins is a high priority and an effort that will be accelerated through 

the Cancer Moonshot.

• DIPG, a type of malignant brain stem tumor, is perhaps one of the most devastating 

cancers diagnosed in children. Most patients die within 2 years of diagnosis. 

However, NCI-funded researchers at St. Jude Children’s Research Hospital and 

the Washington University School of Medicine have recently discovered a specific 

mutation in DIPG tumors that is thought to drive their growth. The mutation affects 

a cell’s ability to normally modify a protein, called histone 3.3, in chromosomes as 

57

a means of controlling gene expression. This finding has led to a clinical trial of the 

drug panobinostat (Farydak®) in children with DIPG. The trial is being conducted 

through the Pediatric Brain Tumor Consortium at ten sites across the country, 

including NCI’s Pediatric Oncology Branch at the NIH Clinical Center. Formed by NCI, 

the consortium facilitates multicenter studies, research, and data sharing to improve 

treatment strategies for children with brain cancers.

• NCI intramural researchers are leading the development of a new targeted therapy 

approach for children with rare tumors, such as neurofibroma tumors, a disease in 

which tumors form in nerve tissue and for which there are no FDA-approved drugs. 

(Read more about this research in the story about Philip Moss of Alabama on page 

59.)

Advance Immunotherapies for the Treatment of Children with Cancer

Despite the remarkable progress made in immunotherapy against adult cancers, 

some immunotherapy approaches have yet to be evaluated for the treatment of 

childhood cancers. With this in mind, NCI will fund research aimed at advancing more 

immunotherapies for childhood cancers to the clinic.

• Major progress in treating childhood acute lymphoblastic leukemia (ALL) with 

genetically modified immune cells called chimeric antigen receptor (CAR) T cells

has researchers hopeful that this type of treatment will represent another major 

approach for children with cancer. One CAR T-cell therapy for childhood ALL is 

already pending approval by FDA, and NCI is sponsoring nearly a dozen clinical trials 

of CAR T-cell therapy in pediatric patients with several other types of cancer.

• In 2017, for the first time, FDA approved several immune checkpoint inhibitors 

for children with cancer. The checkpoint inhibitor pembrolizumab (Keytruda®) 

was approved for pediatric (and adult) patients with classical Hodgkin lymphoma 

that cannot be cured with existing treatments, as well as pediatric (and adult) 

patients with solid tumors that have specific genetic features. (See the story on 

page 52.) Avelumab (Bavencio®) was approved for patients age 12 or older who 

have metastatic Merkel cell carcinoma. FDA expanded its approval of ipilimumab 

(Yervoy®) to include patients age 12 or older who have advanced melanoma. NCI 

supported much of the preclinical and early clinical research that led to the approval 

of ipilimumab. The NCI Experimental Therapeutics Program (NExT) supported the 

early development of pembrolizumab. NCI is also sponsoring early-phase clinical 

trials of pembrolizumab in children with aggressive brain tumors and ipilimumab 

in combination with another immune checkpoint inhibitor in pediatric patients with 

advanced solid tumors or sarcomas. 

• As part of the Cancer Moonshot, NCI is establishing a Pediatric Immunotherapy 

Discovery and Development Network to establish a collaborative research 

network to identify and advance research opportunities for translating 

immunotherapy concepts for children and adolescents with cancer toward clinical 

applications. As stated in the “Developing Precision Immunotherapies” section, the 

goals of the network are to identify new targets for immunotherapies, developing 
58

Treating Cancer

new pediatric immunotherapy treatment approaches, and defining the biological 

mechanisms by which pediatric tumors evade the immune system.

Improve the Long-Term Quality of Life of Survivors of Childhood Cancer

NCI works to reduce the severity of treatment side effects for childhood cancer and to 

identify and address the health problems that may develop many years later, called late 

effects. The Childhood Cancer Survivor Study, funded in part by NCI, has led to a better 

understanding of the late effects of childhood cancer treatments and strategies to reduce 

these adverse effects. More than 35,000 survivors have participated in this study. Among 

the study’s accomplishments was finding that using less cranial radiation to treat acute 

lymphoblastic leukemia (ALL) improves the cognitive abilities of survivors. (Read about 

the experience of childhood cancer survivor and pediatric oncologist Greg Aune, M.D., 

Ph.D., of the University of Texas Health Science Center, San Antonio, on page 61.)

KEY TAKEAWAYS

• NCI funds cutting-edge initiatives in childhood cancer research, including efforts to develop precision medicine and 

immunotherapy treatments, as well as efforts to improve the health and well-being of childhood cancer survivors.

• NCI advances research and facilitates collaboration against childhood cancers, filling an important gap resulting 

from the substantial challenges in conducting this research.

• NCI’s efforts help produce more-effective, less-toxic therapies for all childhood cancers so patients not only survive, 

but thrive.

• NCI’s longer-term goal is to use all data generated from childhood cancer research to identify children and 

adolescents at risk of cancer, detect cancer at the earliest stage, or prevent its development altogether.
5943

When 9-year-old Philip Moss ran 

out of treatment options for his 

neurofibroma tumors in April 2015, his 

doctors directed his family to NCI. NCI 

was leading the only treatment trial in the 

nation for children with tumors caused 

by neurofibromatosis type 1 (NF1), a 

genetic disorder in which painful and 

often disfiguring tumors of the nerves can 

grow on or under the skin. These tumors 

are generally benign, but about 10% of 

people with NF1 will develop a cancerous 

neurofibroma. There are currently no 

Food and Drug Administration-approved 

therapies for NF1.

Philip’s experience with NF1 began when 

he was 6 years old, with the detection, 

diagnosis, and removal of a tumor on his 

neck. “We’d never heard of NF1 before; our 

world changed,” said Renie Moss, Philip’s 

mother. Unfortunately, the tumor regrew 

over the next few years. After additional 

surgery, routine imaging scans revealed 

that the tumor was growing again, and, over 

a 6-month period, it grew from the size of 

a ping pong ball to the size of a tennis ball. 

In addition, other tumors had developed. 

The tumor on his neck was particularly 

concerning because it could obstruct 

his airway or cause other complications. 

“We felt like we were one step away from 

disaster,” recalled Renie.

Philip’s doctor referred them to a 

phase I clinical trial at the NIH Clinical 

Center in Bethesda, Maryland, that was 

testing an experimental targeted therapy 

called selumetinib. The trial was led by 

Brigitte Widemann, M.D., chief of NCI’s 

Pediatric Oncology Branch, and involved 

collaborators from Children’s Hospital of 

Philadelphia, Cincinnati Children’s Hospital 

Medical Center, and the Children’s National 

Health System.

IMPROVING OUTCOMES FOR PATIENTS WITH NF1

Laboratory researchers had previously 

shown that mutations in the NF1 gene 

cause neurofibromas to grow through a 

chemical pathway inside cells called the 

RAS pathway. Selumetinib blocks a specific 

node in this pathway called MEK. In mouse 

models of NF1, MEK inhibitors reduced the 

growth of neurofibroma tumors. Other MEK 

inhibitors are safe and effective in other 

types of adult cancers. Based on these 

findings, researchers hypothesized that 

selumetinib might work in NF1 tumors in 

children.

In September 2015, Philip visited NCI for 

an intense medical evaluation, joined the 

trial, and began taking selumetinib twice 

a day. Because the drug is provided in pill 

form, Philip was able to return home for 

ongoing treatment and was monitored by 

his local pediatrician. He and his family 

learned to cope with the initial side effects 

of treatment, which included fatigue, 

headaches, and nausea. One year after 

joining the trial, Philip’s tumors were 

36% smaller.

Although this trial was a small early-phase 

study, Philip was among the 71% of children 

whose tumor volumes decreased by more 

than 20%. “We saw tumor shrinkage in 

nearly every patient,” Brigitte remarked. 

“The shrinkage was measurable...something 

we had never seen before” among NF1 

patients. These promising results are now 

being pursued in a phase II study.

Philip remains in the trial, and the tumor 

on his neck has shrunk by half. “Kids don’t 

ask what’s wrong with him anymore,” said 

Renie. “It’s meant the world to him and to 

our family.” Renie acknowledged the years 

of research that led to this trial. “Someone 

was planting the seeds in NF1 research so 

we would benefit from that work now.”

PHILIP MOSS

Neurofibroma Survivor

Alabama
60

Treat ing Cance r

JULIE PARK, M.D.

Bushnell, Towne, and Wilkerson 

Endowed Chair in Pediatric 

Neuroblastoma, Seattle Children’s 

Hospital

Professor of Pediatrics, University of 

Washington School of Medicine 

Associate, Clinical Research Division, 

Fred Hutchinson Cancer Research 

Center

USING TANDEM TRANSPLANTS TO TREAT NEUROBLASTOMA

F or many years, less than half of 

children diagnosed with high-risk 

neuroblastoma, a cancer that starts in 

immature nerve cells, would be expected 

to live 5 or more years after diagnosis. 

Pediatric oncologist and researcher 

Julie Park has devoted her career to try 

to change that. In 2016, Julie and her 

colleagues demonstrated encouraging 

improvements using a new approach to 

treat high-risk neuroblastoma in an NCIsponsored clinical trial that changed the 

way the disease is treated in the United 

States. The trial was conducted by the 

Children’s Oncology Group (COG), part of 

NCI’s National Clinical Trials Network.

One of the 652 children who participated in 

the trial was Katie Belle of Seattle, who was 

31⁄2 years old in 2009, when doctors found a 

baseball-sized tumor in her abdomen that 

turned out to be high-risk neuroblastoma. 

Katie was given a 35% chance of survival, 

and, on the advice of doctors, her parents 

immediately enrolled her in the COG trial. 

“When we signed Katie up, there didn’t 

seem to be a lot of novel, promising ideas to 

pursue,” said her mother Jennifer Belle, who 

now serves as a patient advocate on COG’s 

Neuroblastoma Committee.

Before the COG trial, the standard 

treatment for high-risk neuroblastoma was 

a single-transplant approach that involved 

high-dose chemotherapy to destroy as 

many cancer cells as possible, followed by 

an autologous (self-donating) blood stem 

cell transplant. The stem cell transplant is 

needed because the intense chemotherapy 

also destroys blood-forming stem cells in 

the patient’s bone marrow. The stem cells 

used for the transplant are collected from 

the patient’s blood and then given back 

to the patient once the chemotherapy is 

completed. The transplanted cells then 

repopulate the patient’s bone marrow and 

restore its ability to produce red and white 

blood cells and platelets. Prior clinical trials 

conducted by COG demonstrated that this 

treatment approach improved the 5-year 

survival rate for children with high-risk 

neuroblastoma from 25% in the 1990s to 

just less than 50% by the early 2000’s.

The new approach in the recent COG trial 

was to double-up that treatment, with 

the hopes of increasing the percentage 

of patients who would benefit from 

this intense therapy. In the trial, one 

group of patients received the standard 

treatment (chemotherapy and a stem cell 

transplant) and another group received the 

experimental treatment (chemotherapy and 

a stem cell transplant followed by another 

round of chemotherapy and a second, 

or tandem, stem cell transplant). After 3 

years of follow-up, 61% of the patients who 

received a tandem transplant were alive 

and cancer-free, compared with 48% of 

those who received only a single transplant.

Katie was among the patients who received 

a tandem transplant. More than 5 years 

later, she remains cancer free. Although she 

is generally in good health now, Katie did 

experience side effects from the treatment, 

including sterility and thyroid dysfunction. 

Jennifer worries about her future. “We 

don’t know what the other long-term 

complications will be,” she said. Julie added, 

“The therapies for high-risk neuroblastoma 

are among the most toxic therapies given to 

kids.”

Tandem transplants have now become 

the standard of care for high-risk 

neuroblastoma. “Through continued 

research, we keep moving the needle and 

improving survival,” Julie reflected. “The 

next step is to find treatments that will 

be less toxic and more effective.” To this 

end, COG researchers hope to capitalize 

on advances in molecular biology and 

immunology research to find additional 

targets and improve the quality of life for 

children like Katie.
4361

SEARCHING FOR LESS TOXIC TREATMENTS

Advances in cancer treatment mean 

that, today, more than 4 out of 5 

children diagnosed with cancer will survive 

and remain cancer free for at least 5 years 

after diagnosis. Many of these children 

will ultimately be considered cured of 

their cancer. However, the chances of 

either developing a life-threatening health 

problem or dying early as a result of their 

treatment approaches 60% by age 50. 

Potential late effects include cardiovascular 

disease, second cancers, and premature 

menopause.

As a childhood cancer survivor, pediatric 

oncologist, and cancer research advocate, 

Greg Aune knows firsthand that cancer is 

not an acute disease but a lifelong problem. 

At age 16, he was diagnosed with Hodgkin 

lymphoma and was successfully treated 

after undergoing a year of chemotherapy 

and radiation treatments. However, he has 

experienced many late effects from his 

treatment, including infertility, stroke, and 

life-threatening heart disease. “My story 

is one of persistent personal frustration 

with the toxicities of chemotherapy and 

radiation,” said Greg. In fact, his cancer 

experience is what motivated him to 

become a pediatric oncologist and 

physician–scientist.

Anthracyclines, some of the most 

commonly used chemotherapy drugs in 

pediatric oncology, can severally damage 

the heart. Greg’s research focuses on 

identifying biomarkers of toxicity in the 

heart caused by these powerful drugs. 

Understanding this relationship will 

help researchers develop new strategies 

for detecting, preventing, treating, and 

managing cardiac disease in the large 

number of pediatric cancer survivors 

treated with anthracyclines.

The goal of current pediatric oncology 

research is to identify better targeted 

therapies that are less toxic. “My hope is 

that we’re at a point where we can not only 

offer children with cancer an opportunity 

for a cure, but a long life free of debilitating 

health conditions,” said Greg. “In no other 

field of medicine would the late effects we 

see in pediatric cancer be considered an 

unqualified success,” he added.

Until less-toxic therapies are developed, it is 

imperative for health care teams to educate 

the 420,000 U.S. survivors of childhood 

cancer about the possible late effects of 

their treatment and empower them to be 

active participants in their lifelong postcancer health care.

GREGORY AUNE, M.D., PH.D.

Stephanie Edlund Distinguished 

Professor in Pediatric Cancer 

Research and St. Baldrick’s Scholar, 

Greehey Children’s Cancer Research 

Institute, University of Texas Health 

Science Center, San Antonio
ADVANCING 

PUBLIC HEALTH 

IN CANCER
63

Cancer has been recognized as a major public health problem in the United 

States for nearly a century. Today, despite the steady decline in cancer mortality 

observed over the past two decades, it is the leading cause of death from disease 

among Americans under the age of 85. By 2020, it is projected to be the number one 

cause of death from disease among all age groups. However, many cancers and cancer 

deaths can be avoided by maintaining a healthy lifestyle and receiving recommended 

cancer screenings and preventive vaccinations.

NCI supports research focused on improving the delivery of cancer care and designing 

interventions at the individual and population levels to improve cancer prevention, 

screening, treatment, and survivorship. Some areas of opportunity include improving the 

quality of life of cancer survivors; understanding how body weight and physical activity 

influence cancer risk and outcomes; further reducing tobacco use; and delivering highquality cancer prevention, screening, and treatment to all regions of the country.

Improving the Quality of Life of Cancer Survivors

The number of long-term cancer survivors has grown dramatically over the 

past several decades, a trend that is expected to continue as diagnosis and 

treatments improve. Today, approximately 70% of people live 5 years or more 

following a cancer diagnosis, compared with about 50% in the 1970s. In 2016, 

the estimated number of cancer survivors in the United States exceeded 

15 million, more than twice the estimated 7 million in 1992.

In addition to the growing number of survivors, the proportion who are age 

65 years or older will expand rapidly as the U.S. population continues to age. 

By 2040, it is estimated that nearly half of cancer survivors will be age 75 or 

older.

With this increase in survivorship has come an awareness that many cancer 

survivors have health problems, caused by their cancer or its treatment, 

that may require additional and, perhaps, ongoing care. Satisfactorily 

addressing these health problems in older survivors may be complicated by 

the development of other conditions associated with aging. Meanwhile, all 

of this is occurring against a backdrop of projected shortages of oncologists 

and primary care physicians, who are the main providers of medical care for 

cancer survivors.

Consequently, research to understand and find ways to address the unique 

needs of cancer survivors, especially older survivors, is critical and a high 

priority for NCI.

CHALLENGES THAT 

CANCER SURVIVORS FACE

• Risk of recurrence

• Increased risk of second primary 

cancer

• Reduced quality of life

• Economic burden (financial toxicity)

• Treatment side effects (cardiotoxicity, 

cognitive challenges)

• Emotional distress (depression, 

anxiety/uncertainty, altered body 

image, survivor’s guilt)

• Denial of health and/or life insurance

• Physical problems

• Loss of fertility and/or diminished 

reproductive health

• Difficulty maintaining or finding 

employment

• Barriers to health care (high insurance 

and out-of-pocket costs for health care, 

lack of coordination of health care, and 

limited access to specialty care)
Find videos at plan.cancer.gov

64

Advanc ing Publ ic Health in Cance r
65

To make available effective interventions that mitigate the short-term and long-term 

adverse effects of cancer and its treatment and greatly improve the well-being and 

quality of life of cancer survivors

THE VISION

THE APPROACH

• Support research to identify and understand the factors that cause—or increase 

susceptibility to—the short-term and long-term adverse effects of cancer and its 

treatment

• Support research to develop effective interventions to reduce or prevent these adverse 

effects and improve the well-being and quality of life of cancer survivors

Research Priority

Identify and Alleviate the Adverse Effects of Cancer and Its Treatment

Cancer and its treatment are associated with substantial short-term and long-term 

adverse side effects that can diminish the well-being of survivors. NCI funds research 

to develop new treatments that cause fewer adverse effects. In addition, NCI supports 

research to identify factors that cause or increase susceptibility to the harmful effects 

of cancer and its treatment and to develop interventions to reduce or prevent their 

occurrence.

Several examples of NCI’s accomplishments and efforts include:

• NCI’s portfolio of symptom management clinical trials is coordinated through 

the NCI Community Oncology Program (NCORP). NCORP sponsored a clinical 

trial testing duloxetine (Cymbalta®) in breast cancer survivors who were taking 

aromatase inhibitors. Findings from the trial, reported in 2017, showed that 

duloxetine, which is approved to treat depression and anxiety, fibromyalgia, and 

nerve pain caused by diabetes, reduced musculoskeletal pain by an average of 

46%. These findings are important because musculoskeletal symptoms lead some 

patients to discontinue these life-saving aromatase inhibitors.

• The Detroit Research on Cancer Survivors study, launched in 2017, is the 

largest study to date of African-American cancer survivors in the United States. 

It will include 5,560 participants and investigate major factors that affect cancer 

recurrence, mortality, and quality of life among these cancer survivors.

• NCI’s National Clinical Trials Network (NCTN) is developing more trials targeted 

at older patients, particularly those with other health conditions, such as heart 

disease or diabetes. The results of these trials should help doctors develop ageappropriate treatment plans and potentially reduce long-term treatment-related 

side effects. They may also provide much-needed information about resources and 

programs necessary for cancer survivors in long-term recovery.
66

Advanc ing Publ ic Health in Cance r

NCI also supports survivorship research conferences and the development of online 

tools for survivors, including the Springboard Beyond Cancer website. The website is 

a joint venture of NCI and the American Cancer Society, designed to improve survivors’ 

self-management of cancer-related symptoms and treatment side effects, with a focus on 

identifying strategies and skills training. The development of this website was informed 

by cancer survivorship research and health behavior interventions.

KEY TAKEAWAYS

• NCI sponsors research to identify and understand factors that cause or increase susceptibility to the adverse effects of 

cancer and its treatment. 

• NCI-funded researchers are striving to develop effective interventions to reduce or prevent these harmful effects and 

improve the well-being and quality of life of cancer survivors.
67

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Understanding the Influence of Body Weight and 

Physical Activity on Cancer Risk and Outcomes

Numerous epidemiologic studies have linked obesity and physical inactivity with 

increased risks of more than a dozen types of cancer. Research also suggests that 

physically active cancer survivors have fewer or less-severe side effects from treatment 

and an improved quality of life compared with those who are inactive. Associations 

between exercise and reduced rates of cancer recurrence and mortality have also been 

reported. However, more research is needed to understand the biological mechanisms by 

which body weight and physical activity influence cancer risk and patient outcomes. This 

knowledge can then be translated into effective interventions.

THE VISION

To prevent more cancers and improve the quality of life of survivors by reducing obesity 

and physical inactivity

THE APPROACH

• Support research to better understand how body weight and physical activity influence 

cancer risk and outcomes for cancer patients and survivors

Research Priority

NCI funds a wide range of research to learn how body weight and physical activity modify 

cancer risk and outcomes, and NCI-funded researchers use the acquired knowledge to 

design and test new interventions.

Understand the Effects of Weight and Physical Activity on Cancer Risk and 

Patient Outcomes

The biological mechanisms by which body weight and physical activity influence cancer 

risk and patient outcomes are not well understood. Moreover, traditional epidemiologic 

studies are limited in their ability to determine how strongly these factors influence 

cancer-related outcomes because they rely on people’s ability to accurately recall or 

record their weight at specific ages as well as their dietary intakes and amounts of 

physical activity over time. Consequently, stronger study designs, such as randomized 

controlled trials when feasible, and more accurate survey instruments are needed. 

Therefore, NCI supports research in the laboratory and the clinic to address these issues, 

with the goal of ultimately translating the knowledge gained into effective interventions 

for those at risk of cancer and for cancer survivors.

Examples of NCI-funded research in this area include:

• The Transdisciplinary Research on Energetics and Cancer (TREC) initiative, which 

catalyzed research on the biological, behavioral, sociocultural, and environmental 

influences that affect nutrition, energy balance (the ratio of calories consumed 
68

Advancing Public Healt h in Cancer

to calories burned), body weight, physical activity, and cancer risk. TREC, which 

was funded in 2005 and 2010, enabled the creation of research partnerships that 

otherwise would not have been possible. Some TREC studies incorporated animal 

and human models to identify and understand the relevant biomarkers and 

physiological effects of exercise, sedentary behavior, diet, and, cancer. The role of 

sleep in obesity and energy balance was also explored.

Two of the many research advances that have emerged from TREC are:

 An increased understanding of how obesity influences chemotherapy 

effectiveness: TREC researchers at the Children’s Hospital Los Angeles and 

the University of Southern California developed novel preclinical models 

to understand the mechanisms underlying the increased risk of relapse 

observed among obese children with acute lymphoblastic leukemia (ALL). 

They determined that adipocytes (fat cells) impair the response of leukemia 

cells to chemotherapy in a manner that is independent of cell–cell contact. 

These findings have led to a clinical trial of personalized dietary and exercise 

interventions in children and adolescents with newly diagnosed ALL to reduce 

body fat and improve treatment responses.

 A greater understanding of the potential for exercise to reduce the 

increased risk of breast cancer associated with delayed childbearing: 

Research support from TREC enabled a team of researchers from the University 

of Pennsylvania, Harvard University, Washington University in St. Louis, and 

Kaiser Permanente Northern California to develop an animal model to study 

the protective effects of exercise on the breast cancer risk associated with 

delayed childbearing. The researchers found that exercised rats had a longer 

time to tumor development, a smaller tumor burden, and less abnormal 

proliferation of breast tissue (ductal hyperplasia) than rats that had not been 

exercised.

Other TREC accomplishments include new statistical modeling methods, a system for 

coding health messages in the media, new dietary measurement tools, and databases 

for physical activity and sleep measures. Ongoing research is exploring whether 

obesity, which is a risk factor for postmenopausal breast cancer, influences immune cell 

populations in the breast tumor microenvironment. Ideas for another TREC renewal (i.e., 

TREC 3) are currently in development.

• Weight loss, diet, and exercise interventions for cancer survivors to identify 

those interventions that are most effective and understand how they influence 

outcomes for survivors. The randomized Lifestyle, Exercise, and Nutrition (LEAN) 

Study, described on page 69, highlights this type of research. 

KEY TAKEAWAY

• NCI sponsors research that will increase the understanding of how diet, body weight, and physical activity influence 

cancer incidence and outcomes and translate the knowledge gained into effective interventions for cancer patients, 

survivors, and those at risk.
6943

RUNNING (AND EATING) AWAY FROM CANCER

S ue Wharfe was diagnosed in 2011 with 

stage II breast cancer. Her doctors at 

Yale Cancer Center, where she received 

treatment, referred her to a research study 

on nutrition and exercise for breast cancer 

survivors. Sue jumped at the chance to 

participate. She hoped it would help her to 

lose weight and improve her diet. “I was the 

type of person who would join a gym, feel 

good about joining, but then never go. I had 

good intentions but following through with 

them was a challenge,” she explained.

Research shows that obesity is associated 

with worse survival from breast cancer, 

but more research is needed to develop 

and implement methods to help cancer 

survivors make positive lifestyle changes. 

Sue was one of 100 women who 

participated in a study led by Melinda Irwin, 

Ph.D., M.P.H., professor of epidemiology 

at Yale University, aiming to address this 

question. The study—called the Lifestyle, 

Exercise, and Nutrition Study, or LEAN—

showed that in-person and telephone 

counseling led to clinically significant 

weight loss among participants. The 

researchers also gained clues about the 

biological effects of weight on breast cancer. 

Participants who received counseling 

experienced a 30% decrease in C-reactive 

protein, a marker of systemic inflammation 

that is associated with poorer outcomes in 

women with breast cancer. 

Sue was randomly assigned to the in-person 

intervention. With encouragement from the 

registered dietician and oncology nutrition 

specialist assigned to her in the study, Sue 

took up running with a friend, starting with 

20 minutes a day, and began to feel the 

benefits of the activity in about 3 weeks. 

From a diet that contained too much fat, 

she switched to a “rainbow plate” with more 

fruits and vegetables. She benefited from 

the intervention, which supported her as 

she was trying to lose weight, a change she 

appreciates to this day. 

The changes also helped with the stiffness 

and achiness in her joints that accompanied 

her aromatase inhibitor therapy, which 

she recently learned she needs to continue 

taking for another 5 years. In fact, additional 

NCI-funded research by Melinda’s team 

found that exercise reduces joint pain 

associated with aromatase inhibitors.

LEAN was enabled by NCI’s Cancer Center 

Support Grant to Yale, which provides 

resources to support exceptional clinical 

care and conduct transdisciplinary research. 

Melinda is appreciative of NCI, which 

has enabled her to conduct some of the 

largest trials investigating the interactions 

between weight, diet, and physical activity in 

relation to cancer. She is also part of NCI’s 

Transdisciplinary Research on Energetics 

and Cancer (TREC) initiative. “NCI is the only 

organization that provides longer-term 

funding to support this type of research, 

which aims to change paradigms with the 

goal of lowering people’s risk of developing 

or dying from cancer,” said Melinda.

Sue can attest to the efficacy of this 

intervention. Years later, she continues to 

jog and eat healthfully, still mindful of the 

better behaviors she learned from Melinda’s 

study. Her good habits have rubbed off 

on her husband and kids, too. She doubts 

she would have made these lifestyle 

improvements without LEAN. “It has led to a 

better, healthier life,” she added.

SUE WHARFE

Breast Cancer Survivor

Connecticut
70

Advancing Public Healt h in Cance r

Reducing Tobacco Use Before and After a Cancer 

Diagnosis

At least 20 different types of cancer have been linked to tobacco use, and more than 

160,000 cancer deaths each year in the United States are attributable to smoking. Major 

reductions in tobacco use among American adults—from a high of 42% of the adult 

population in 1965 to about 15% today—have lowered the number of deaths from lung 

cancer and other tobacco-related diseases; however, lung cancer still claims more lives 

among U.S. men and women than any other cancer type.

Cancer patients who continue to smoke after diagnosis may face additional tobaccorelated harms. For example, NCI-funded research has shown that continued smoking 

increases the risk of second cancers in patients with head and neck cancer, increases 

risks of recurrence and reduced survival in patients with prostate cancer, and increases 

risks of death from breast and respiratory tract cancers in women diagnosed with breast 

cancer. Other NCI-funded research has shown that cancer patients who continue to 

smoke experience a greater burden of treatment-related side effects than nonsmokers, 

which may lead to treatment interruptions, reductions in treatment doses, and delays 

in treatment that can, in turn, compromise treatment effectiveness and reduce survival. 

However, more research is needed to fully understand the impact of continued smoking 

on cancer patients, particularly on the effectiveness of cancer therapy.

Additional research and resources are also needed to further reduce the harms of 

tobacco use among individuals who have not been diagnosed with cancer, especially 

those in at-risk populations for tobacco uptake, including the young and the 

socioeconomically disadvantaged.

THE VISION

To eliminate smoking, and the cancers and other harms it causes, to improve public health

THE APPROACH

• Support research on tobacco prevention and cessation interventions—especially those 

aimed at vulnerable populations, including the young and the socioeconomically 

disadvantaged, who are at increased risk of tobacco use

• Support research to implement and sustain evidence-based tobacco cessation 

programs, in cancer centers and other medical settings, to reduce tobacco use by 

cancer patients

Research Priorities

Support Research on Tobacco Prevention and Cessation

To help guide NCI’s tobacco control research agenda through the year 2025, the 

institute established the Tobacco Control Research Priorities Working Group in 2015. 

This group, led by Michael Fiore, M.D., M.P.H., M.B.A., of the University of Wisconsin 
71

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

School of Medicine and Public Health, presented its report to NCI’s Board of Scientific 

Advisors in 2016. (Read about Michael’s perspective on page 72.) The working group’s 

recommendations included a call for focused efforts to improve the effectiveness and 

accessibility of tobacco prevention and cessation interventions and to discourage tobacco 

use by vulnerable populations. NCI is well positioned to support the working group’s 

recommendations.

Implement Effective Tobacco Prevention and Cessation Interventions

The development and implementation of effective tobacco cessation interventions 

for cancer patients and those at increased risk of cancer is a high priority for NCI. For 

example, the institute: 

• Supports tobacco cessation at NCI-Designated Cancer Centers: Evidencebased tobacco cessation interventions designed for individuals without cancer

should be offered as part of the coordinated care of all cancer patients. However,

comprehensive tobacco cessation programs are not currently available at all NCIDesignated Cancer Centers that provide patient care services. Therefore, NCI is

making supplemental funding available to help cancer centers plan, implement,

evaluate, and sustain tobacco cessation programs for cancer patients who smoke.

In addition, NCI has awarded grants to six cancer centers to conduct research on

the design and implementation of tobacco cessation interventions for patients

undergoing lung cancer screening with low-dose CT scans.

• Hosts the Smokefree.gov website to make information and resources about

smoking cessation available to the public, health professionals, and researchers. In

2016, 4.5 million smokers interacted with Smokefree.gov.

KEY TAKEAWAY

• NCI supports research to develop and implement evidence-based measures to reduce the use of tobacco products

among all individuals, including populations that are vulnerable to the initiation of tobacco use and patients who are

undergoing or have completed active cancer treatment.
72

Advanc ing Publ ic Health in Cance r

MICHAEL FIORE, M.D., 

M.P.H., M.B.A.

Hilldale Professor of Medicine, 

University of Wisconsin School of 

Medicine and Public Health 

Founder and Director, University 

of Wisconsin Center for Tobacco 

Research and Intervention

WORKING TO REDUCE THE CANCER BURDEN CAUSED

BY TOBACCO

Every year, 70% of smokers in the United 

States visit a health care professional. 

Many, however, leave without receiving 

any smoking cessation assistance. 

Approximately half of smokers diagnosed 

with cancer continue to smoke, and only 

some health care centers provide these 

patients with services to quit. “This is a 

missed opportunity to help people become 

healthier and live longer,” said physician 

and researcher Michael Fiore.

Tobacco use in the United States continues 

to cause unparalleled harm to the nation’s 

health, directly causing one out of every five 

deaths. Moreover, tobacco causes at least 

20 different types of cancer, including up to 

90% of all lung cancers. Cigarette smoking 

is the main culprit, being responsible for 

more than 480,000 deaths per year in this 

country, including nearly 42,000 deaths 

from exposure to secondhand smoke. 

Michael predicts that “eliminating smoking 

in America would, over time, reduce all 

cancer deaths by almost one-third.”

As a leader in tobacco control, Michael 

helped to spearhead a working group of 

the NCI Board of Scientific Advisors that 

recommended research priorities for this 

field. The group’s 2016 report discussed 

a wide range of research gaps. One of 

these was optimizing the effectiveness 

of the evidence-based tobacco cessation 

interventions that already exist. The 

report also highlighted groups that 

disproportionately bear the burden of 

cancer and other health consequences of 

continued tobacco use.

NCI has a long history of supporting tobacco 

control research and launched several new 

activities in 2017 relevant to the priorities 

the working group identified. These include 

additional funding to NCI-Designated 

Cancer Centers to bolster smoking 

cessation activities and focused efforts to 

reduce tobacco use by vulnerable groups, 

including the young, the socioeconomically 

disadvantaged, and individuals with mental 

health issues or HIV.

Michael is hopeful about NCI’s response 

to the working group’s recommendations 

and commitment to reducing the cancer 

burden in the United States. “Recognizing 

that tobacco use is a chronic disease—and 

not just a bad habit—informs our ongoing 

research to identify and implement the best 

prevention and cessation strategies,” he 

said.
73

Delivering High-Quality Cancer Care to All Americans

NCI supports research to understand and improve how cancer care is delivered in the 

United States. The ultimate goal of this research is to ensure that high-quality cancer care 

is available and accessible to all Americans wherever they live.

Developing, implementing, and sustaining state-of-the-art cancer prevention, screening, 

and treatment programs for rural populations, will be particularly challenging. Rural 

populations often face substantial barriers in accessing quality health care due to a 

shortage of doctors, lengthy distances to medical facilities, limited transportation options, 

and other factors. In addition, rural populations frequently have high rates of tobacco 

use, poverty, poor health literacy, and drug and alcohol abuse, which contribute to higher 

cancer risks and poorer health outcomes.

THE VISION

To make state-of-the-art cancer care available and accessible to all Americans

THE APPROACH

• Support research to identify factors that influence cancer care delivery in all regions of 

the United States and its territories

• Support research to improve the delivery of high-quality cancer care to the American 

public

Research Priority

Identify and Address Factors that Influence the Delivery of Quality Cancer Care 

NCI supports research on the delivery of cancer care through its Healthcare Delivery 

Research Program and the NCI Community Oncology Research Program. This 

research includes studying barriers to the implementation of evidence-based cancer 

prevention, screening, and treatment methods; recommended follow-up care for cancer 

survivors; and psychosocial support programs for patients and their caregivers. The 

ultimate goal of this research is to optimize the delivery of high-quality cancer care to all 

Americans, thereby helping to reduce the burden of cancer in the United States. Some of 

NCI’s activities in this area include:

• Supporting telecommunications research on the use of broadband technologies 

to promote improved cancer prevention and care in both rural and urban areas. 

This research, for example, led to the online program A Smoking Prevention 

Interactive Experience (ASPIRE), which is aimed at middle and high school 

students. 

• Working with other organizations through the Centers for Disease Control and 

Prevention’s National Comprehensive Cancer Control Program (NCCCP). NCI and 

the other NCCCP members support comprehensive cancer control activities in U.S. 

states, territories, Pacific Island jurisdictions, and tribes and tribal organizations. 
74

Advancing Public Healt h in Cancer

Activities include efforts to increase HPV vaccination uptake, increase colorectal 

cancer screening, and increase availability of tobacco cessation services for cancer 

survivors—areas that are described in previous sections of this Annual Plan and 

Budget Proposal.

• As NCI strengthens its efforts in cancer control and prevention, the needs of Native 

American and Alaska Native populations are particularly important. These 

populations have unique needs and concerns that can be challenging to address. 

For example, Native Americans and Alaska Natives have higher incidence and death 

rates from certain cancers than other populations groups. This population is diverse, 

and culturally relevant prevention and early detection efforts are needed. NCI is 

working to address these needs.

KEY TAKEAWAY

• NCI supports health care delivery research, infrastructure, and partnerships that will increase accessibility to highquality cancer care to all individuals in the United States, including those in minority and underserved 

rural populations.
7543

“F or people struggling to make 

ends meet, the last thing on their 

minds is health care,” said Electra Paskett, 

who has devoted her 30-year career to 

addressing cancer disparities experienced 

by underserved groups in the United States. 

“The question we want to answer is how to 

reach them,” she said.

Electra’s efforts to address cancer 

disparities through science and community 

partnerships, which NCI has supported over 

the last two decades, have led to important 

improvements in cancer screening and care 

in rural and low-income populations where 

cancer rates have remained stubbornly 

high. Populations in the Ohio Appalachian 

region and inner-city African Americans, in 

particular, have benefited from her studies.

In the Appalachian areas of Ohio, Kentucky, 

Pennsylvania, Virginia, and West Virginia, 

the rates of lung, cervical, and colorectal 

cancer incidence and mortality are higher 

than anywhere else in the United States. 

“It’s all about figuring out why,” said Electra. 

To identify the causes of these disparities 

and develop ways to reduce them, she 

conducts research to develop and test 

interventions.

Her approach includes partnership 

building with local clinicians and public 

health officials and, most importantly, 

with members of the community. “The 

people who live there in those communities 

know what strategies work best for them,” 

explained Electra. This community-based 

participatory research approach means 

she often takes road trips into the heart of 

Appalachian country.

In these less-populous areas, she meets 

with locals, listens to their stories, and asks 

for their perspectives on how to address 

ADDRESSING CANCER DISPARITIES IN APPALACHIA

their higher-than-average cancer incidence 

and mortality rates. With their assistance, 

Electra has successfully pinpointed public 

health flaws and gaps.

Her research has tested such initiatives as 

working with local churches to promote 

healthy eating and exercise, conducting 

outreach to parents and clinicians to 

improve rates of HPV vaccinations among 

adolescent girls, and implementing 

mammogram vans to make breast cancer 

screening more accessible. By working 

with communities and implementing 

culturally sensitive strategies, Electra has 

found that people will be more proactive 

about their health needs and even adopt 

healthier behaviors, such as regular cancer 

screenings, when appropriate programs 

and incentives are put into place.

ELECTRA PASKETT, PH.D.

Director and Marion N. Rowley 

Professor of Cancer Research, Division 

of Cancer Prevention and Control, 

The Ohio State University College of 

Medicine
STRENGTHENING THE 

CANCER RESEARCH 

ENTERPRISE
77

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

NCI leads the national effort against cancer in many ways. NCI sustains the 

cancer research workforce through training and research grant support. The 

institute also supports infrastructure to care for patients and conduct clinical 

trials, prevent cancer and develop better treatments by understanding the biological 

and molecular mechanisms that promote cancer growth, and promote data sharing to 

hasten progress in cancer research for all Americans and the rest of the world. Resources 

developed by NCI help investigators maximize their research efforts. Research at NCI 

focuses on high-risk studies and areas of unmet need. Together, these efforts are aimed 

at improving cancer prevention, detection, and treatment, with the goal of producing 

better outcomes for patients and those at risk for cancer.

Supporting Scientists at Every Career Stage 

A strong workforce of researchers who are passionate about cancer research and are 

well-supported can make discoveries faster and translate them more efficiently into 

new ways to prevent, detect, and treat cancer. To address this need, NCI supports a 

diverse scientific workforce over the course of their careers—as high school, college, 

and graduate students; research and clinical fellows; early career researchers; and 

established investigators. NCI supports individual investigators as well as collaborative 

research teams.

Training the Next Generation of Cancer Researchers

NCI supports the next generation of cancer scientists, who will make the paradigmshifting discoveries of the future.

• The middle and high school years are important in shaping students’ perceptions 

about possible future careers, and two programs showcase how NCI is providing 

training opportunities to students at this impressionable stage.

 The Continuing Umbrella of Research Experiences (CURE) program 

promotes diversity in the cancer and cancer health disparities research 

workforce by providing training and career development support for 

underrepresented minorities. CURE emphasizes mentorship, provides 

protected time to gain research experience, and creates training opportunities 

to develop career skills. CURE provides support to high school students and 

to undergraduate and graduate students, and in 2014, the program began 

engaging students at the middle school level. Over the past two decades, the 

program has supported more than 3,000 scholars from almost every state 

across the country. (Read about former CURE trainee Chanita Hughes-Halbert, 

Ph.D., of the Medical University of South Carolina, on page 86.)

 The Werner H. Kirsten Student Intern Program has brought more than 1,000 

high school students to NCI’s campus in Frederick, Maryland, for a summer 

internship that continues part-time throughout their senior year. The interns 

gain hands-on laboratory research training or experience in scientific support 

areas, including communications and information technology. More than half 

of the students in the program have gone on to careers in health, medicine, 

science, or education. The program recently celebrated its 25th anniversary 
78

Strengthening the Research Enterprise

and received an Award of Excellence from the Maryland State Department of 

Education in 2017.

• The NCI Predoctoral to Postdoctoral Fellow Transition Award (F99/K00) helps 

graduate students who are near the end of their graduate education and wish 

to pursue a research career move into postdoctoral studies. The program helps 

students to develop a well-defined career path more quickly by preparing them 

for other awards that will lead to independent, tenure-track, or equivalent faculty 

positions.

Investing in Early-Career and Established Investigators

Everything NCI does focuses on supporting the best science to improve the outlook for 

patients and their families. To do this, NCI seeks to recruit outstanding investigators and 

provide them with support throughout their careers in cancer research. A few ways in 

which NCI does this include:

• Focusing on investigator-initiated research: More than 40% of the total NCI 

budget supports research project grants, an important mechanism for advancing 

the ideas of an individual or small group of investigators at all stages of their 

career. Supporting investigator-initiated research is a high priority for NCI because 

the unique insights and expertise of investigators allow research to expand into 

previously unforeseen but potentially productive areas. Between 2013 and 2015, 

NCI increased support for new awards from $400 million to $500 million per year 

and continues to sustain the increase. In addition, 2015 and 2016 were the first 

years since 2004 and 2005 that NCI provided full support for noncompeting grants 

(funding for the next budget period within an approved project period) for 2 years 

in a row. This support is greatly valued for assuring continued advancement in all 

areas of cancer research.

• Supporting new and early-stage investigators: Scientists starting independent 

research positions are at a critical stage in their careers. NCI supports these 

innovators of the future through grants, such as mentored career development 

awards, and other activities designed to enhance their ability to succeed in cancer 

research. One new activity, the principal investigator workshops conducted by NCI’s 

division leadership and program staff, connects new R01 grant recipients with NCI 

staff responsible for administering their grant. Approximately 20%–24% of all R01 

awards are provided to new and early-stage investigators, and 40% of R21 grant 

awards are made to new investigators.

• Finding new approaches to fund researchers: The NCI Outstanding Investigator 

Award (R35), which is given to principal investigators who have a history of 

significant research accomplishments and outstanding productivity, is an example 

of a new approach to fund researchers. The R35 award provides stable funding for 

a longer period than that afforded by a traditional R01 award. The funding stability 

provided by this award encourages accomplished investigators to take on higherrisk and potentially higher-reward research projects. The R35 program began in 

fiscal year (FY) 2015 with awards made to 43 prominent investigators, followed by 35 

new awards in FY 2016 and 43 in FY 2017.
79

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Providing Infrastructure and Resources for Cancer 

Research and Patient Care

NCI supports the cancer research community through an infrastructure that connects 

investigators working at major academic research centers, in community settings, within 

NCI and other federal agencies, and at private-sector companies. NCI’s collaborative 

efforts with partners across the community put patients at the forefront by ensuring that 

scientists and clinical researchers are equipped to make discoveries and test ideas that 

advance cancer research and clinical care across the United States.

Sustaining NCI-Designated Cancer Centers

The NCI-Designated Cancer Centers Program constitutes a major component of the 

national cancer research enterprise. NCI-Designated Cancer Centers meet rigorous 

standards for research focused on developing new and better approaches to cancer 

prevention, diagnosis, and treatment. Acquiring the “NCI-designated” status is a major 

achievement, and cancer centers that receive it are highly valued by their communities 

because they are recognized as providing state-of-the-art, evidenced-based cancer 

care. There are currently 69 of these cancer centers in the United States. In recent 

years, NCI has increased the size of the Cancer Center Support Grants that support the 

infrastructure needed by researchers at a cancer center—such as centralized shared 

resources—and that create a focused transdisciplinary research environment. The 
80

Strengthening the Research Enterprise

program was established with a vision of having an NCI-Designated Cancer Center within 

200 miles of every person residing in the United States.

Facilitating Cancer Clinical Trials

NCI has a long history of supporting all phases of clinical trials, from small early-phase 

trials that seek to determine the safety of new interventions to large trials that compare 

new interventions with the current standard approach.

• NCI’s National Clinical Trials Network (NCTN) serves as the cornerstone of 

the institute’s clinical trial enterprise. NCTN provides streamlined mechanisms 

for conducting cancer clinical trials throughout the United States. The network 

includes five U.S. clinical trial research groups and several international member 

sites that contribute to the approximately 2,400 NCTN sites enrolling patients in 

clinical treatment trials, including precision medicine clinical trials such as the NCI 

Molecular Analysis for Therapy Choice (NCI-MATCH) and NCI-COG Pediatric MATCH 

trials.

Examples of NCTN trials with recently reported results include:

 A trial demonstrating that, after 10 years of follow-up, progression-free and 

overall survival were 30% and 20% longer, respectively, for patients with 

grade 2 glioma who received combination chemotherapy and radiation therapy 

compared with patients who received radiation therapy alone.

 A trial, called the Trial Assigning IndividuaLized Options for Treatment (Rx), 

or TAILORx, showing that women with estrogen receptor–positive early-stage 

breast cancer who have a low risk of recurrence based on a 21-gene expression 

assay can forgo chemotherapy and the associated side effects and be safely 

treated with hormone therapy alone.

• The NCI Community Oncology Research Program (NCORP) is a network of 

institutions that conducts research and clinical trials in community-based health 

care systems. Launched in 2014, NCORP is comprised of 46 community sites. Twelve 

of these sites focus on minority and underserved communities, including patients 

who live in rural areas and cannot travel far distances to receive treatment at an 

NCI-Designated Cancer Center. (Read more about one of these sites in the story 

about Chanita Hughes-Halbert, Ph.D., of the Medical University of South Carolina, on 

page 86.) NCORP participation accelerated the pace of enrollment in the NCI-MATCH 

trial and helped to reach traditionally underrepresented rural populations. NCORP 

builds on previous NCI programs to bring clinical trials and cancer care delivery 

research into the community, where most cancer patients—approximately 85%—are 

treated.
81

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Providing Resources to Advance Research

NCI develops and maintains resources to help researchers prevent, diagnose, and treat 

cancer, including databases and specimen repositories, cancer-related tools, and other 

materials that are available to scientists and the public via NCI’s website. The following 

represent just two of these kinds of resources.

• The Surveillance, Epidemiology, and End Results (SEER) Program facilitates the 

collection and analysis of cancer statistics at the population level. SEER serves as the 

authoritative source of information on cancer incidence and survival in the United 

States. The program oversees the only population-based cancer registries in the 

country that include a broad set of clinical elements, with the registries located 

at or associated with NCI-Designated Cancer Centers. NCI manages the program 

and collaborates with other organizations, including the American Cancer Society 

and the Centers for Disease Control and Prevention, to make SEER a success. 

Furthermore, SEER data are used extensively to support research beyond NCI, 

with 4,000 downloads of its public-use files annually. For example, researchers use 

SEER to track trends in cancer at the national, state, and local levels; understand 
82

Strengthening the Research Enterprise

factors that influence these trends; and describe cancer disparities among different 

populations.

• The NCI Natural Products Repository holds more than 80,000 natural products 

obtained from all over the world and makes the products and their extracts available 

to academic and industry researchers. The products and extracts are screened 

for anticancer activity and used in the development of cancer drugs and for other 

medical uses. NCI’s leadership role in natural products has increased as industry 

has begun to focus on screening synthetic (laboratory-made) chemicals, which 

are easier to analyze than the complex mixtures of chemicals present in natural 

products, which need to be fractionated further for study. To promote the use of 

natural products in this modern era of drug development, NCI is generating 

1 million extracts for high-throughput cancer drug screening. As seen in the story on 

the development of eribulin mesylate on page 85, this unique resource harnesses 

the power of nature to identify and develop new drugs to treat and prevent cancer, 

which is fundamental to ensuring the health of many Americans.

Strengthening Small Business Innovation 

and Commercialization

NCI provides funding and support to drive the development and commercialization of 

novel technologies and products to prevent, detect, and treat cancer.

• NCI’s Small Business Innovation Research (SBIR) and Small Business Technology 

Transfer Research (STTR) Programs are two of the largest sources of financing 

for early-stage technology in the United States. Small businesses are a national 

resource for technological innovation and a mainstay of the economy. These 

programs strengthen their role in federally supported research and development 

by providing funding, mentoring, and networking assistance to small businesses 

and researchers, like Avrum Spira, M.D., M.Sc., of Boston University. (Read about the 

lung cancer screening test Avrum developed on page 36.) NCI also helps connect 

researchers with government scientists who can help them develop promising 

cancer drugs, diagnostics, and devices. In addition, SBIR fosters participation by 

minority and socially disadvantaged companies in technology innovation.

• The I-CorpsTM at NIH program, which is led by NCI in collaboration with the Centers 

for Disease Control and Prevention (CDC), supports training that will help project 

teams at NIH- and CDC-funded small businesses overcome key obstacles along the 

path of innovation and commercialization.

Conducting Research at NCI

Although the overwhelming majority of NCI’s budget funds extramural research—that 

is, research conducted in laboratories and clinics throughout the United States—the 

national cancer research enterprise also includes work done by scientists at laboratories 

and offices located primarily on the National Institutes of Health (NIH) campus and 

surrounding locations in suburban Maryland.
83

NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2019

Intramural Research Program

NCI’s intramural research program (IRP) conducts long-term, high-risk research and 

clinical trials that would be more difficult for the extramural community or industry 

to complete. The IRP allows NCI to focus on emerging public health concerns and 

contributes to the training of the next generation of researchers in basic, clinical, 

translational, and epidemiologic research. IRP basic and clinical researchers at NIH’s 

Mark O. Hatfield Clinical Research Center and Warren Grant Magnuson Clinical Center 

collaborate to provide compassionate patient care and unparalleled opportunities for 

advancing cancer research.

A few examples of IRP accomplishments include:

• Developing treatments for rare tumors, including the 2017 approval of avelumab 

(Bavencio®), the first drug approved by the Food and Drug Administration (FDA) for 

Merkel cell carcinoma, a rare but deadly skin cancer.

• Pioneering adoptive cell transfer immunotherapy, in which a patient’s own 

cancer-fighting immune cells are extracted from their tumor, grown in large 

numbers in the laboratory, and then infused into the patient. This research has been 

applied in several clinical trials and is expected to be used more widely in the clinic 

in the next several years.

• Conducting basic scientific research on the human papillomavirus (HPV), which led 

to FDA-approved HPV vaccines and major advances in the prevention of cervical 

cancer and other cancers caused by HPV.

• Identifying risks associated with tobacco use, including the finding in 2016 that 

low-intensity smokers (those who smoked an average of less than one cigarette per 

day over their lifetimes) had an increased risk of early death, including death from 

lung cancer, compared with people who never smoked.

• Detecting risk-factor status for multiple types of cancer, including Helicobacter 

pylori infection and gastric cancer, discoveries that have led to the development of 

risk stratification models and clinical interventions to prevent or treat cancer.

Frederick National Laboratory for Cancer Research

The Frederick National Laboratory for Cancer Research is a government-owned, 

contractor-operated national laboratory that is dedicated exclusively to biomedical 

research. It is the Department of Health and Human Service’s only federally funded 

research and development center. The Frederick National Lab offers unique partnering 

opportunities for academia, government, and the private sector to address the most 

difficult challenges in cancer prevention and treatment.

Major initiatives and partnerships of the Frederick National Lab include:

• The RAS Initiative, launched in 2013, which is exploring innovative approaches to 

attack the proteins produced by mutant forms of members of the RAS gene family. 
Find videos at plan.cancer.gov

84

A cryo-electron microscopy (cryoEM) map of a protein created at the 

National Cryo-EM Facility hosted by 

the Frederick National Laboratory for 

Cancer Research

Credit: National Cancer Institute

Strengthening the reSearch enterpriSe

The goal of the initiative is to develop effective therapies for RAS-related cancers. 

Because more than 30% of all human cancers—including 95% of pancreatic cancers 

and 45% of colorectal cancers—are driven by mutations in RAS genes, understanding 

the biology of RAS proteins is critical to finding better treatments for patients.

• The Accelerating Therapeutics for Opportunities in Medicine (ATOM) 

Collaboration, which is a partnership formed in 2017 by NCI, the Department of 

Energy, GlaxoSmithKline, and the University of California, San Francisco, to leverage 

their strengths in computational biology to dramatically accelerate the discovery 

and development of new cancer drugs.

• The National Cryo-Electron Microscopy (cryo-EM) Facility, which was opened 

at the Frederick National Lab in 2017, to capitalize on revolutionary changes in the 

cryo-EM field that allow researchers to capture exceptional imaging resolution at the 

near-atomic level. The facility is designed to meet the needs of cancer researchers 

who are engaged in structural biology cryo-EM research but do not have access to 

the latest technologies at their own institutions.

• NCI leads programs to build, sustain, and diversify the cancer research workforce. This includes supporting the next 

generation of investigators, established researchers, and collaborative team science.

• NCI provides critical infrastructure that brings state-of-the-art cancer care and the benefits of clinical trials to more 

people.

• NCI conducts research and provides research resources that cannot or will not be provided by others.

• NCI advances the commercialization potential of scientific discoveries through support to small businesses.

• NCI supports unmet needs in cancer research through its intramural program and national laboratory.

KEY TAKEAWAYS
8543

I

n 2016, the Food and Drug 

Administration (FDA) approved the first 

drug that improved the survival of patients 

with liposarcoma—a drug made possible by 

a sea sponge. This drug, eribulin mesylate 

(commonly called eribulin or Halaven®), was 

also approved in 2010 for certain patients 

with breast cancer. The story of how a 

sea sponge led to a cancer drug spans 

three decades of NCI-supported research 

and collaboration among governments, a 

pharmaceutical company, and universities.

The medicinal properties of natural 

products, including plants and marine 

organisms, have long been a productive 

source of “lead” molecules for researchers 

developing cancer drugs. In fact, many 

cancer drugs are based on natural 

products, including paclitaxel (Taxol®) 

from the Pacific yew tree for breast and 

ovarian cancers and vinblastine (Velban®) 

and vincristine (Marqibo®) from another 

plant, the rosy periwinkle, for childhood 

leukemias and other cancers. In fact, a 

recent review of drug approvals has shown 

that 49% of all cancer drugs approved by 

FDA from around the 1940s to the end of 

2014 were derived from natural products.

In 1986, Japanese researchers reported on 

a group of compounds called halichondrins, 

isolated from the sea sponge Halichondria 

okadai, that had promising anticancer 

activity. Subsequently, a team of NCI 

intramural and extramural investigators 

discovered that one of the halichondrins 

from this sponge and other sponge types 

from the Pacific blocked cell growth by 

inhibiting the protein tubulin, confirming 

its anticancer potential and demonstrating 

its mechanism of action. NCI worked with 

institutions in New Zealand to obtain a 

supply of this halichondrin for testing. 

Because it was present in such small 

amounts in the sponges, NCI-funded 

FIGHTING CANCERS WITH A SEA SPONGE

researchers, led by Yoshito Kishi, Ph.D., 

of Harvard University, developed a way to 

generate the halichondrin in the laboratory.

Recognizing halichondrin’s potential against 

cancer, a pharmaceutical company licensed 

the compound and made a series of 

modified versions, or analogs, for testing. 

Positive results from the tests led to the 

development of one of the analogs, which 

became known as eribulin, in collaboration 

with NCI. NCI supported the preclinical 

studies and early clinical trials of eribulin, 

and the company subsequently tested the 

drug in large phase III clinical trials.

NCI’s extensive work and investment, as 

well as the interplay of academia, industry, 

and government, played important roles in 

developing and bringing eribulin to market 

over the course of two decades. NCI-funded 

scientists demonstrated that eribulin was 

as efficacious as pure halicondrin and could 

be provided in more sufficient quantities. 

This persuaded a pharmaceutical company 

to continue its studies and development 

of eribulin and ultimately brought an 

effective therapy to cancer patients who 

had otherwise exhausted their treatment 

options.
86

Strengthening theResea rch Enterprise

CHANITA HUGHES-HALBERT, 

PH.D.

AT&T Distinguished Endowed Chair in 

Cancer Equity, Medical University of 

South Carolina

BRINGING RESEARCH TO THE COMMUNITY TO 

REDUCE DISPARITIES

Approximately 85% of cancer patients 

in the United States receive care 

in community settings, not at academic 

medical centers where most clinical 

trials take place. This is certainly true in 

South Carolina, where Hollings Cancer 

Center at the Medical University of South 

Carolina (MUSC) serves as the state’s 

only NCI-Designated Cancer Center.

More than 30% of the people in South 

Carolina are minorities, and more than 

40% live in rural areas. These individuals 

can often face logistical and financial 

challenges when trying to access clinical 

trials. For example, for someone who 

lives several hours from MUSC, receiving 

care there would take an entire day. “A 

lost day’s work equals a lost day’s pay” 

for many people in South Carolina, said 

Chanita Hughes-Halbert, a nationally 

recognized leader in cancer disparities 

research and behavioral science at MUSC.

Being able to join research studies in a 

person’s own community allows them 

to miss less time at work, stay close 

to family and friends, and reduces the 

burden of participation in research 

while increasing the quality of their care. 

To enhance patient access to clinical 

trials and facilitate the participation of 

community providers in cancer research, 

NCI launched the NCI Community 

Oncology Research Program (NCORP) in 

2014. Forty-six community sites comprise 

NCORP, each of which partners with 

other cancer care providers in their 

region. 

Twelve of the NCORP sites are minority/

underserved community sites that have

STRENGTHENING THE RESEARCH ENTERPRISE
8743

patient populations of at least 30% 

racial/ethnic minorities or rural 

residents. One of the minority/

underserved sites is MUSC, which 

brought together community care 

organizations across the state as a 

result of its NCORP grant. Chanita 

leads the NCORP site along with public 

health researcher Marvella Ford, Ph.D., 

and hematologist/oncologist Carolyn 

Britten, M.D. The NCORP grant created 

a “team spirit” among the collaborating 

organizations and is facilitating 

interaction among researchers in 

different disciplines that traditionally 

are siloed, said Chanita. 

Enhancing participation of patients in 

precision medicine trials is particularly 

important, Chanita said, because 

finding and subdividing patients into 

distinct groups based on the genomic 

characteristics of their tumors is “like 

looking for a needle in a haystack.” She 

added, “A national effort is required to 

increase the pace of this research and 

for it to be successful.” 

As evidence of this, NCORP sites 

are playing a critical role in the NCI 

Molecular Analysis for Therapy Choice 

(NCI-MATCH) trial, in which patients are 

assigned to receive treatment based 

on the genetic changes in their tumors. 

The number of patients in the trial 

increased from 3,000 to 6,000, thanks 

to increased resources provided by 

NCI’s regular appropriation.

The trial reached its goal of sequencing 

the tumors of 6,000 patients in June 

2017, nearly 2 years sooner than 

expected due to wide-scale adoption 

of the trial throughout NCORP and 

NCI’s National Clinical Trials Network 

(NCTN). The unprecedented rate of 

patient enrollment was accomplished 

by more than 1,100 academic centers 

and community hospitals in all 50 

states and Puerto Rico and is reaching 

traditionally underrepresented rural 

populations.

The MUSC NCORP grant is supporting 

enhanced access to clinical trials with 

a focus on minority and underserved 

communities with the goal of reducing 

cancer disparities. “Efforts to enroll 

more diverse patients helps ensure that 

we don’t get to the end of trials and 

realize we won’t be able to understand 

how treatments will work in different 

populations,” concluded Chanita.
Find videos at plan.cancer.gov

88