LANDMA

Decades of Breakthroughs in Cancer Research and Treatment

RKS

Center for Cancer Research

U.S. Department of Health & Human Services | National Institutes of Health
TABLE OF 

CONTENTS

NOTE FROM THE DIRECTOR 2

CCR BY THE NUMBERS 3

THE HPV VACCINE 4

DISCOVERY OF TGF-β 6

CHROMATIN PIONEERS 8

CYTOKINES AS THERAPY 10

DEVELOPMENT OF CANCER IMMUNOTHERAPY 12

GENOMIC CLASSIFICATION OF TUMORS 14

CELLULAR IMAGING 16

THE FIRST AIDS DRUGS 18

PRECISE CLINICAL IMAGING OF TUMORS 20

AWARDS AND ACCOLADES 22

SELECTED REFERENCES 24

CENTER FOR 

CANCER RESEARCH 

The Nation’s Cancer Center

As part of the federally funded National Cancer Institute (NCI), the Center 

for Cancer Research (CCR) is the nation’s cancer center. Located in the 

suburbs of Washington, D.C., our scientists are unlocking the mysteries 

of cancer and discovering new ways to prevent, diagnose and treat it. 

The CCR collaborates with academic and commercial partners and 

advocacy groups across the world in efforts to find treatments and cures 

for cancer through basic, clinical and translational research. Our physicianresearchers translate these discoveries from the lab to the clinic, and we 

treat thousands of people from around the country every year with novel 

therapies through our clinical trials program at the National Institutes of 

Health Clinical Center. For more about our science, our training programs 

and our clinical trials, visit ccr.cancer.gov.

The MISSION of the CCR is to improve the 

lives of cancer patients by solving important, 

challenging and neglected problems in 

cancer research, prevention and patient care 

through: 

• A world-leading basic, translational and clinical research and 

patient-care program

• An institutional focus on high-risk and long-term projects, unmet 

needs and pursuit of unexplored ideas

• Leadership and coordination of national disease networks and 

development of technology resources for the cancer community

• Partnerships with academic institutions, commercial entities and 

patient advocacy groups

• Training of the next generation of the biomedical workforce
4 4 5

Tom Misteli

Director, NCI Center for Cancer Research

The NCI Center for Cancer Research is at the forefront of cancer research – and has 

been for decades. Work from our basic and clinical investigators has led to fundamental 

insights into biological processes, the development of new cancer drugs, innovative 

vaccines and groundbreaking technologies that enable basic discovery and are used in 

the clinic every day to diagnose and treat patients. 

In this publication we highlight some of our landmark discoveries over the years. They 

span the spectrum from basic research on how genes are expressed in cancer cells to 

advances in clinical care. They represent impactful research that has shaped and changed 

scientific fields and led to novel clinical applications that benefit patients. The remarkable 

discoveries highlighted in this magazine are a testimony to the creativity, ingenuity and 

persistence of CCR investigators. They are also a reminder of the extraordinary return on 

investment of federal funds allocated to maintaining and improving the well-being of 

our nation.

Why has CCR been so successful for so long? The short answer is that we do cancer 

research differently from most institutions. We have created an environment where our 

investigators can freely pursue what they consider to be the most important problems 

in cancer biology and treatment, and they can do so with limited time pressure. The 

intellectual freedom afforded to CCR scientists and the technological resources 

available to support them are unmatched. They enable projects that may be considered 

excessively risky in an academic or commercial setting but that fill an important niche in 

the biomedical landscape. The CCR’s distinctive environment also combines basic and 

clinical research under one roof to foster interdisciplinary research to tackle the most 

difficult problems in cancer research.

Our science is driven by our curiosity and by our commitment to better lives. While we 

have reached many landmarks along the way, what motivates and inspires us is the 

knowledge that much remains to be done to prevent, diagnose and treat cancer. New 

landmarks are ahead, and we strive to reach them every day through our work in CCR.

NOTE FROM 

THE DIRECTOR

CCR BY 

THE NUMBERS (AVERAGE PER YEAR)

87 New 

Employee 

Invention 

Reports

158 Active Cooperative 

Research and Development 

Agreements (CRADAs) 

411 Clinical 

trials

52Issued 

U.S. patents

~1500 Articles in 

peer-reviewed journals

614 Active 

licenses

32 New trials 2214 opening

New 

patients

~1000 Trainees

CCR PRODUCTS:

VACCINES AND THERAPEUTICS

2-F-Ara-Fludara, Berlex

Videx®, Berlex

Hivid®, BMS

Paclitaxel®, BMS

Trimetrexate- Neu Trexin, US Bioscience

Zenapax®, Hoffman La Roche

Vitravene®, Isis Pharma

Zevalin®, IDEC Pharma

Kepivance®, Amgen

Gardasil®, Merck

Prezista®, Tibotec Pharma

Cervarix®, GSK

*Avelumab, Pfizer

*Istodax®, Celgene

*Voraxaze®, BTG

*Avastin®, Genentech

*YescartaTM, Kite Pharma

*CCR clinical trial testing

DIAGNOSTICS

Diagnostic test for HIV-1

Diagnostic test for HTLV-1

DNA Probe for Breast Cancer

Multi-Replica Blotting Kit for Proteins

INSTRUMENTATION/DEVICES

Laser Capture Microdissection

UroNav

ccr.cancer.gov
Little did CCR researchers 

Doug Lowy, M.D., and 

John Schiller, Ph.D., know 

in the 1990s that their 

studies of two cancercausing genes would lead 

to the first commercially 

available vaccine against 

the two deadliest forms of 

the cancer-causing human 

papillomavirus (HPV). Today, 

these powerfully effective 

vaccines have slashed HPV 

infection rates by 64 percent 

in the United States. As 

vaccination rates go up, 

there is already evidence 

of the potential to nearly 

eliminate HPV-caused 

cervical cancer in women 

coming of age and to 

prevent many other 

HPV-related cancers in 

both men and women.

In the 1980s, the 

connection between 

specific types of the HPV 

virus and cervical cancer 

became increasingly clear 

due to a series of laboratory 

and epidemiological 

studies conducted by NCI 

researchers and others. 

By the early 1990s, these 

discoveries inspired Lowy 

and Schiller to focus their 

research on developing a 

vaccine. Even though neither 

had prior experience in the 

field, they relied on the 

infrastructure of the NCI 

intramural program and 

its culture of intellectual 

freedom that allowed 

them to pursue high-risk, 

long-term projects. 

Lowy and Schiller had 

previously studied two 

cancer-causing genes, or 

oncogenes, in the HPV 

genome that produce 

proteins, named E6 and E7, 

that can cooperate to render 

human cells cancerous. 

They knew that the 

presence of the oncogenes 

would complicate vaccine 

development. While vaccines 

at the time often used 

weakened or killed viruses, 

in this case, using any form 

of authentic HPV could 

potentially introduce the 

oncogenes into patients. 

In their first attempt to 

develop a papillomavirus 

vaccine, the team discovered 

an alternative to using an 

intact virus in the vaccine. 

Remarkably, they found 

that multiple copies of 

the HPV protein L1 could 

spontaneously assemble 

into non-infectious viruslike particles (VLPs). Upon 

injection, these VLPs 

stimulated production of 

large quantities of antibodies 

and prevented viral infection 

in animal models. The 

VLPs were subsequently 

shown to be safe and highly 

immunogenic in trials 

THE 

HPV VACCINE

4

Caption: Doug Lowy, M.D., and 

John Schiller, Ph.D., developed 

technology that led to vaccines 

against the two deadliest forms 

of cancer-causing HPV.

Credit: Rhoda Baer

ccr.cancer.gov

with human volunteers. 

These encouraging results 

attracted the interest of the 

pharmaceutical companies 

Merck and GlaxoSmithKline 

(GSK), who licensed the 

technology from CCR. 

By 2006, interim results 

from a company-sponsored 

trial were so promising 

that the U.S. Food and 

Drug Administration (FDA) 

approved Merck’s Gardasil 

for the prevention of cervical 

cancer and genital warts in 

women before the trial had 

finished. In 2009, Gardasil 

was approved for use in 

men to prevent anal cancer 

and genital warts, and GSK’s 

Cervarix was approved for 

use in women to prevent 

cervical cancer. 

After a decade on the 

market, HPV vaccines have 

been shown by numerous 

studies to successfully 

prevent infection by the HPV 

types known to cause most 

cervical cancers in nearly 

all vaccinated women. The 

vaccines also offer a strong 

potential for protection 

against vaginal, vulvar, anal, 

penile and head and neck 

cancers in members of both 

sexes. 

Lowy, Schiller and their 

colleagues continue to 

be involved in research to 

prevent HPV infection and 

the cancers they cause in 

both women and men. In 

2014 they were awarded 

the National Medal of 

Technology and Innovation 

for their work. In 2017 

they were awarded the 

Lasker-DeBakey Clinical 

Medical Research Award for 

technological advances that 

enabled development of 

HPV vaccines for prevention 

of cervical cancer and other 

tumors caused by the human 

papillomaviruses.

In 2017 Lowy and Schiller received the Lasker-DeBakey Clinical Medical 

Research Award for their groundbreaking research. In announcing 

the award, the Lasker Foundation found that Lowy and Schiller “took a 

bold but calculated approach toward a major public health problem whose 

solution required them to vault formidable hurdles.“ 

5
In 1981, CCR scientists 

discovered a molecule 

that both promotes and 

inhibits cellular growth. By 

thoroughly characterizing 

that molecule, which 

they called transforming 

growth factor (TGF)-β, they 

demonstrated how different 

biological contexts can alter 

a signaling molecule’s effect 

and revealed how TGF-β

might be exploited to treat 

cancer. Nearly 25 years after 

the molecule’s discovery, the 

first drugs designed to treat 

cancer by inhibiting TGF-β

signaling entered clinical 

trials. Today, many 

such drugs are being 

evaluated in clinical 

trials for the treatment 

of cancer and other 

diseases.

NCI scientists, led by 

Michael Sporn, M.D., and 

Anita B. Roberts, Ph.D., in 

the 1980s, found TGF-β in 

cancerous cells and showed 

that it could make healthy 

cells malignant. Soon after, 

however, they made an 

unexpected discovery. They 

found that noncancerous 

cells produced the tumorpromoting factor too. To 

solve this puzzle, the NCI 

investigators undertook a 

major effort to isolate TGF-β

from human blood cells and 

shared the purified 

protein with researchers 

around the world in the 

hope of elucidating its 

role in cancer. 

Their subsequent 

experiments yielded 

surprising results. They 

confirmed that TGF-β can 

cause excessive cell growth, 

but in some situations 

they found it suppresses 

growth. The opposing 

functions made it difficult to 

imagine how to treat cancer 

by manipulating TGF-β

signaling. However, Sporn, 

Roberts and their colleagues 

eventually exposed TGF-β’s 

complex effects on cancer 

cells as well as its key roles 

in wound healing and 

immunity. 

Because of its interactions 

with context-dependent 

signals, TGF-β generally 

promotes the growth and 

metastasis of advanced 

cancers but protects against 

early tumor formation. 

Working in animal models, 

CCR’s Lalage Wakefield, 

D.Phil., who trained under 

Sporn and Roberts, later 

demonstrated that it is 

possible to block the tumorpromoting effects of TGF-β

without affecting its normal 

tumor-suppressing activity. 

6

Caption: Anita Roberts, Ph.D., 

and Michael Sporn, M.D., 

discovered TGF-β’s complex 

effects on cancer cells, wound 

healing and immunity.

Credit: NCI, NIH

ccr.cancer.gov

The discovery and 

characterization of TGF-β

is one of CCR’s many 

contributions to the 

deep understanding that 

scientists now have of 

cancer’s elaborate signaling 

networks—knowledge that 

drives the development of 

targeted treatments. 

Other CCR breakthroughs 

in cancer signaling include 

studies of the oncogene 

HRas by Doug Lowy, M.D., 

which demonstrated how 

mutations can convert a 

gene involved in normal 

growth regulation into a 

driver of cancerous growth; 

the discovery by George 

Vande Woude, Ph.D., that 

overactive signaling from 

the Met gene renders cells 

tumorigenic and metastatic; 

and the demonstration by 

Stuart Aaronson, M.D., that 

the HER2 gene can cause 

normal cells to behave like 

aggressive cancer cells. 

These genes can be critical 

lynchpins in different 

signaling networks and 

are the targets of several 

approved cancer treatments, 

as well as experimental drugs 

now under investigation. 

DISCOVERY 

OF TGF-β

Patients who receive high doses of conventional chemotherapy and radiation can suffer from 

painful ulcers in their mouths and throats that increase the risk of infection and make eating, 

drinking and speaking difficult. Thanks to the discovery of a growth-promoting molecule called 

keratinocyte growth factor (KGF) by CCR investigator Jeff Rubin, M.D., Ph.D., this side effect, known 

as oral mucositis, is now treatable. A modified version of KGF, called palifermin (Kepivance), speeds 

the healing of ulcers in the mouth and throat. In 2004, it was approved by the U.S. FDA for the 

prevention of oral mucositis. The drug also enables patients with blood cancers to better tolerate 

intensive cancer treatments prior to bone marrow transplants.

7
For much of the 20th 

century, scientists were 

fascinated by DNA. They 

probed its roles in gene 

activity and genetic 

inheritance using genetics, 

biochemistry and molecular 

biology. Most of these 

studies were conducted 

with DNA in its iconic 

double-helix formation. 

Meanwhile, it was well 

known that DNA in intact 

cells exists in a much more 

complex form known as 

chromatin, with many 

proteins required for its 

packaging. However, 

chromatin was mostly 

thought of as a means to 

package an organism’s 

genetic material and was 

not assumed to have any 

other functional significance. 

Taking full advantage of their 

abilty to explore provocative 

ideas, NCI investigators 

pioneered the study of 

chromatin and demonstrated 

its functional importance. 

In all but the simplest 

organisms, DNA is wrapped 

around packing proteins 

known as histones. 

A portion of DNA winds 

around eight histones to 

form a recurring structure 

called a nucleosome. 

In the mid-1980s, NCI 

researcher Gordon Hager, 

Ph.D., uncovered the first 

evidence that nucleosomes 

are carefully and predictably 

positioned along regulatory 

regions of DNA. 

Analyzing DNA near 

a hormone-activated 

gene, Hager showed 

that nucleosomes there 

corresponded precisely 

to sites bound by 

that hormone, 

suggesting they 

had 

a role 

in gene 

regulation. 

In fact, he found organized 

nucleosomes were essential 

for correct hormonetriggered gene activation. 

The findings led to the now 

well-accepted idea that the 

gene-activating hormone 

receptor might trigger 

functionally important 

CHROMATIN 

PIONEERS 8

Caption: An enzyme repairs a 

broken DNA strand.

Credit: Tom Ellenberger, 

Washington University School 

of Medicine in St. Louis; Dave 

Gohara, St. Louis University 

School of Medicine

ccr.cancer.gov

chromatin changes. 

How that reconfiguration 

happened remained a 

mystery. 

NCI biochemist Carl Wu, 

Ph.D., solved this puzzle. 

His laboratory demonstrated 

that chromatin adopts its 

more open configuration 

when a gene-activating 

transcription factor binds 

to its DNA. Later, Wu’s 

lab discovered a protein 

complex called NURF that 

drives that change, shoving 

nucleosomes aside to make 

way for the enzyme that 

reads the DNA. 

Since Hager and Wu’s 

early discoveries, scientists 

at NCI and elsewhere 

have continued to find 

unexpected complexity 

in chromatin’s structure, 

function and biological 

impact. They’ve learned 

that chromatin is an active 

environment where enzymes 

and regulatory molecules 

grab on and then flit away; 

they have discovered 

that RNA molecules are 

critical regulators of 

chromatin; and they 

have defined how chromatin 

is reshaped to allow repair 

proteins access to the 

genome. 

NCI scientists’ discoveries 

about chromatin’s function 

in healthy cells have 

laid the groundwork for 

understanding chromatin’s 

role in cancer and other 

diseases. Today, researchers 

are finding that mutations 

that disrupt chromatin are 

common in human tumors, 

and researchers are working 

to unravel the consequences 

of these changes.

CHROMATIN 

AND EPIGENETICS

Researchers in the field 

of epigenetics, which 

looks at changes in gene 

expression not due to the 

genetic code itself, are 

working to understand 

the full impact of these 

chemical marks and the 

cellular and environmental 

factors that influence 

them. Alterations 

in the form of epigenetic 

marks in a genome can 

have major consequences 

for cellular function, and 

many such changes have 

been linked to disease. 

9
Cytokines are small 

proteins that carry messages 

between cells and are 

known to play a critical role 

in the body’s response to 

inflammation and immune 

attack. CCR researchers 

pioneered the therapeutic 

use of a class of cytokines 

called interleukins. In 

collaboration with academic 

and commercial partners 

across the country, CCR 

scientists have successfully 

led the translation of 

several interleukins with 

demonstrated therapeutic 

potential from the lab to 

the patient.

Interleukin-2 (IL-2), the first 

cytokine found to have 

therapeutic benefit, was 

discovered in 1976 by Robert 

Gallo, M.D., and Francis 

Ruscetti, Ph.D. The team 

demonstrated that this 

cytokine could dramatically 

stimulate the growth of T 

and natural killer (NK) cells, 

which are integral to the 

human immune response. 

This seminal work enabled 

researchers to grow and 

study T cells in the laboratory 

for the first time, changing 

the field of immunology 

forever.

Nearly a decade later, 

researchers led by Steven 

Rosenberg, M.D., Ph.D., 

successfully cured several 

patients with advanced 

metastatic renal cell 

cancer and melanoma by 

administering IL-2. It became 

the first U.S. FDA-approved 

cancer immunotherapy 

and is still used in clinical 

settings to treat metastatic 

melanoma and renal cancer. 

CCR researchers are currently 

investigating whether 

combining IL-2 with other 

cytokines is effective in 

treating patients with 

these cancers. 

CCR research groups led 

by Crystal Mackall, M.D., 

and Ron Gress, M.D., 

characterized another 

cytokine, IL-7, as a 

master regulator of T-cell 

homeostasis or equilibrium. 

CYTOKINES 

AS THERAPY

Conducted groundbreaking studies leading to 

the development of monoclonal antibodies Cloned the alpha subunit of the IL-2 receptor 

Discovered IL-2 and demonstrated it is a T-cell 

growth factor

Used IL-2 to develop the first effective 

immunotherapy cancer treatment

10

ccr.cancer.gov

In the first human clinical 

trial with IL-7, they found 

that the cytokine drives 

regeneration of T cells 

that are critical to the 

immune system but 

become depleted during 

chemotherapy. IL-7-based 

therapies also might restore 

immune function in other 

immunocompromised 

individuals, such as those 

with HIV and the aged, and 

might enhance the activity 

of vaccines and other cancer 

immunotherapies (see 

Development of Cancer 

Immunotherapy, p.12).

A third cytokine, IL-15, was 

co-discovered in CCR in 

1994 by Thomas Waldmann, 

M.D., and his team. Like IL-2, 

it triggers the production 

of immune cells that attack 

and kill cancer cells. CCR 

collaborated with the 

NCI’s Division of Cancer 

Treatment and Diagnosis 

and the National Institute 

of Allergy and Infectious 

Diseases to produce 

clinical-grade IL-15 for 

first-in-human testing 

in clinical trials across 

the U.S. Coming 

full circle, it was 

Waldmann’s group 

that initiated the 

first IL-15 clinical trial 

in 2011. The results 

of the trial, published 

in 2015, showed IL-15 

dramatically increased 

growth and activity of 

T and NK cells. Studies 

investigating the potential 

for IL-15 to enhance the 

effectiveness of vaccines 

against viruses that cause 

cancer and autoimmune 

diseases are underway. 

The success CCR researchers 

have had in developing 

therapeutic cytokines is 

a reflection of the highly 

collaborative nature 

of CCR research, both 

among NIH colleagues and 

with academia and the 

commercial sector. 

Caption: A colorized scanning 

electron micrograph of 

a T lymphocyte used in 

immunotherapy.

Credit: National Institute of 

Allergy and Infectious Diseases, 

NIH

11

Discovered and cloned the first chemokine, IL-8 Co-discovered IL-15 

Created a single chain recombinant 

immunotoxin 

Discovered JAK3 and demonstrated it is 

activated by IL-2 
More than 30 years ago, NCI 

intramural scientists began 

to explore the heretical idea 

that a patient’s immune 

system could be harnessed 

to fight cancer. The objective 

was to amplify and unleash 

the body’s natural ability to 

recognize and destroy cancer 

cells. The resulting field, now 

called immunotherapy, has 

made important advances 

in cancer treatments using 

monoclonal antibodies and 

cytokines, as well as cellbased therapies. 

CCR scientist Michael 

Potter, M.D., conducted 

groundbreaking research 

that led to the development 

of monoclonal antibodies, 

for which he received the 

1984 Albert Lasker Award for 

Basic Medical Research. His 

findings laid the foundation 

for the use of monoclonal 

antibodies to successfully 

treat several types of cancer.

One approach, developed by 

CCR researcher Ira Pastan, 

M.D., coupled a monoclonal 

antibody to a toxin to deliver 

it to cancer cells. The resulting 

immunotoxin has been an 

effective therapy for 

patients with hairy cell 

leukemia and has shown 

promise in the treatment 

of other hematologic 

cancers, as well as liver and 

mesothelin-based cancers. 

Monoclonal antibodies have 

also become the agent of 

choice to block key immune 

checkpoints, which limit 

the capacity of the body 

to kill cancer cells. In 2003, 

CCR investigator Steven 

Rosenberg, M.D., Ph.D., 

was amongst the first to 

show that checkpoint 

blockade drugs could lead 

to cancer regression. This 

approach is now used 

worldwide in the treatment 

of many types of cancers.

In the mid-1980s, Rosenberg 

discovered that treating 

cancer patients with the 

cytokine interleukin-2 (IL2) reduced or eliminated 

tumors in some patients. 

Several other cytokine-based 

DEVELOPMENT 

OF CANCER 

IMMUNOTHERAPY 

Demonstrated that the immunotoxin BL22 

induced remission in hairy cell leukemia 

Reported first successful gene therapy of any 

cancer in humans 

Showed the administration of a checkpoint 

inhibitor can mediate cancer regression 

Determined T cells expressing CARs could be 

used to successfully treat cancer 

12

ccr.cancer.gov

therapies developed by 

CCR researchers soon 

followed (see Cytokines 

as Therapy, p. 10). 

Rosenberg’s team went 

on to pioneer cell-based 

cancer therapies by using 

IL-2 in a different capacity. 

T cells, which are key 

infection-fighting cells in 

the body, were isolated 

from a patient’s tumor and 

grown in the laboratory with 

IL-2, a potent T-cell growth 

factor. These cells were 

then re-infused into the 

patient. While this proved an 

effective treatment for some 

patients, the researchers 

discovered they could 

improve these results by 

genetically engineering T 

cells to recognize proteins 

specific for the patient’s 

cancer cells. 

One outcome of these early 

adoptive cell therapy studies 

was the development of 

chimeric antigen receptor 

(CAR) expressing T cells. 

T cells isolated from a 

patient’s blood are modified 

to express a CAR that will 

ideally enable the cell to 

recognize and destroy 

specific types of cancer 

cells. Rosenberg’s team 

was the first to show that 

CAR T cells recognizing 

CD-19 are useful in the 

treatment of some blood 

cell cancers.

While the initial components 

necessary to develop CAR 

T-cell treatments were 

painstakingly developed at 

NCI, they are now widely 

used, and numerous 

laboratories have since 

demonstrated the benefits 

of this approach in the 

treatment of a variety of 

cancers. What started 

decades ago as a speculative 

idea in CCR laboratories is 

now common practice in 

hospitals around the world.

Caption: Steven Rosenberg, 

M.D., Ph.D., with Linda Taylor, 

the first cancer patient he cured 

using immunotherapy.

Credit: NIH Record

13

First use of IL-7 to treat cancer in humans 

Reported epithelial cancers can be successfully 

treated using adoptive cell therapy

Developed method to identify and target unique 

mutations in cancer cells from individual patients 

First-in-human clinical trial of IL-15
While it is current practice 

today to molecularly 

characterize tumors based 

on their genetic fingerprints, 

CCR investigators were 

among the first to classify 

tumors based on genetics. 

As a result, treatments are 

now being tailored to an 

individual’s specific cancer 

subtype, and new therapies 

are being developed to 

target the vulnerabilities of 

different types of cancer 

cells. Major CCR successes 

in this area have improved 

the classification of kidney 

cancers and lymphomas and 

have laid the foundation for 

what is now called precision 

medicine.

Historically, kidney cancer 

was considered a single 

disease with a poor 

prognosis in its advanced 

stages. Hoping to find clues 

about the disease’s origins 

that might lead to targeted 

therapies, CCR investigators 

Marston Linehan, M.D., and 

Berton Zbar, M.D., set out 

in the 1980s to search for its 

genetic causes. 

They established a 

hereditary cancer program 

to recruit patients with rare 

genitourinary cancers to 

the NIH Clinical Center and 

launched large-scale genetic 

studies. After analyzing 

the DNA of thousands of 

patients, the team linked 

mutations in the VHL gene 

to the von Hippel-Lindau 

syndrome that predisposes 

people to developing 

tumors in many organs, 

including the kidneys. The 

VHL gene is also commonly 

mutated in non-inherited 

cases of clear cell renal 

cell carcinoma, the most 

common type of kidney 

cancer. Understanding the 

VHL pathway has provided 

the foundation to develop a 

number of novel approaches 

to therapy for this disease.

Linehan and his colleagues 

went on to identify and 

characterize a number of 

different genes that are 

mutated in different forms of 

kidney cancer. Determining 

which mutations are present 

helps doctors predict how 

aggressive a patient’s 

cancer is likely to be and 

assists in recommending 

an appropriate treatment. 

Identifying the pathways 

disrupted by these 

mutations has also pointed 

toward strategies for 

developing new therapies, 

including immunotherapy. 

In the 1990s, CCR 

investigator Louis Staudt, 

M.D., Ph.D., began searching 

for molecular distinctions 

that might predict the 

clinical course of an 

aggressive blood cancer 

called diffuse large B cell 

GENOMIC 

CLASSIFICATION 

OF TUMORS

14

ccr.cancer.gov

lymphoma (DLBCL). DLBCLs 

look the same under the 

microscope, and although 

some patients respond 

well to chemotherapy, no 

one could predict who 

might benefit from a more 

aggressive approach. 

Taking advantage of CCR’s 

support for open-ended 

discovery, Staudt created 

a novel DNA microarray 

termed the lymphochip 

and used it to analyze the 

activity of thousands of 

genes in tumor biopsies 

from patients with DLBCL. 

Interrogating their data, 

the team identified two 

main subtypes of DLBCL, 

each with a characteristic 

molecular profile that is 

now recognized as a distinct 

cancer type by the World 

Health Organization. The 

discovery explained why 

patients respond differently 

to chemotherapy and 

enabled researchers to 

develop new strategies 

for eliminating the more 

difficult-to-treat subtype, 

activated B-cell (ABC) 

DLBCL. 

Most significantly, this 

discovery coincided with the 

development of the drug 

ibrutinib that specifically 

inactivated an enzyme called 

BTK, which Staudt showed is 

a lynchpin in the ABC form of 

the disease. In clinical trials 

conducted with Wyndham 

Wilson, M.D., Ph.D., a 

close colleague of Staudt, 

patients with ABC DLBCL 

had frequent responses 

to ibrutinib, some quite 

durable, whereas ibrutinib 

was ineffective against most 

other DLBCL tumors. Staudt 

and Wilson are extending 

this precision medicine 

paradigm to other forms of 

lymphoma and are devising 

combination regimens that 

are tailored to the molecular 

abnormalities of each 

lymphoma subtype.

Technology developed by CCR investigators Lance Liotta, M.D., Ph.D., Robert Bonner, Ph.D., and 

Michael Emmert-Buck, M.D., Ph.D., in 1996 paved the way for the large-scale molecular analysis of a 

range of cancers. The method, called laser capture microdissection, enables the isolation of tumor 

cells from the surrounding normal tissue in a sample to help determine the genetic difference 

between the two. As researchers view the sample through a microscope, they trace the desired cells 

with a laser. This allows for the precise separation of tumor cells from the healthy or precancerous 

tissue that surrounds them. The technique was an important step forward for genomic classification 

because it damages neither the structure of the cell nor its chemistry. It also leaves surrounding 

cells intact, thereby enabling extraction of pure cells from the desired location. 

15

Caption: Marston Linehan, 

M.D., discusses treatment with 

a patient. Linehan is a pioneer 

in the study of the genetic basis 

of kidney cancer.

Credit: Rhoda Baer
A unique aspect of CCR 

is an interest in the 

development of new 

methods and technology 

to drive discovery. 

Innovative imaging methods 

developed and refined 

within CCR have revealed 

atomic-level structures 

of biological molecules 

and unveiled dynamic 

views of a cell’s interior. 

These technologies have 

enabled groundbreaking 

discoveries at the 

subcellular level that 

are driving the design 

of new treatments 

and diagnostics for 

cancer.

For decades, X-ray 

crystallography has 

been the primary 

mainstay of structural 

studies of biological 

molecules. The technique 

has yielded molecular 

structures at a very high 

resolution but only worked 

optimally with molecules 

that could be crystallized 

without destroying the 

integrity of the molecule 

itself. CCR investigator 

Sriram Subramaniam, Ph.D., 

and his team have now made 

it possible to obtain the 

same type of high-resolution 

structural information for 

many molecules that are 

incompatible with X-ray 

crystallography through 

his use of cryo-electron 

microscopy, or cryo-EM. 

Cryo-EM could become 

an important part of 

accelerating drug discovery. 

It was named “Method of the 

Year” by Nature in 2015 and 

in 2017, was recognized by 

the Nobel Prize in Chemistry.

To visualize molecules with 

cryo-EM, purified proteins 

are flash-frozen in liquid 

nitrogen and bombarded 

with electrons to capture 

a molecular image. In 

2015, the Subramaniam 

laboratory reported the 

highest-resolution image 

ever produced with the 

technique, visualizing the 

structure of a bacterial 

enzyme with a level of detail 

previously achieved only 

with X-ray crystallography. 

Since then, his group has 

produced extraordinarily 

high-resolution structures 

that offer insight into how 

potential targets for new 

cancer therapies work and 

interact with compounds 

that block their function. 

This type of information is 

expected to help guide the 

design of new drugs for 

patients. 

16

Caption: This composite image 

of the beta-galactosidase 

molecule shows how cryo-EM’s 

resolution has dramatically 

improved in recent years.

Credit: Veronica Falconieri, 

Sriram Subramaniam, CCR, 

NCI, NIH

ccr.cancer.gov

To fully understand a 

biological molecule’s 

involvement in health or 

disease, scientists also 

need to understand how 

it behaves in its natural 

context. In the early 2000s, 

the laboratory of Tom Misteli, 

Ph.D., started devising 

methods to visualize how 

genes behave in living 

cells. The group developed 

techniques using fluorescent 

tags to observe generegulating proteins in action 

and used the tags to show 

that the protein activities are 

surprisingly dynamic. They 

also created complementary 

approaches to track the 

locations and motion of 

genes themselves. Those 

tools led to the discovery 

that genes have particular 

three-dimensional positions 

within the cell nucleus and 

their spatial organization has 

a profound impact on their 

level of activity. In 2009, 

Misteli’s team discovered 

that some genes reside in 

different places inside cancer 

cells than in noncancerous 

cells. Following these 

displaced genes may one 

day help clinicians diagnose 

disease.

The imaging and visualization 

methods developed by CCR 

scientists have propelled 

studies of the mechanisms 

that drive cancer and have 

influenced imaging as 

well as other aspects of 

diagnostic and clinical areas 

of oncology. As researchers 

have proven, when the 

unseen becomes visible, our 

understanding of biology 

gains sharper focus.

CELLULAR 

IMAGING

Diagnostic labs around the world rely on a method developed at CCR to visualize chromosomes 

and diagnose disease. The method, developed by Thomas Ried, M.D., in 1997, is called spectral 

karyotyping (SKY). It paints different chromosomes with distinctly colored fluorescent probes so 

that each one can be easily identified. SKY is particularly useful in cancer cells, whose broken and 

mixed up chromosomes can make other methods of chromosome identification nearly impossible. 

17
Faced with the burgeoning 

HIV/AIDS epidemic in the 

1980s, NCI’s intramural 

program developed the 

first therapies to effectively 

treat the disease. The 

NCI efforts drew upon its 

established expertise in 

virology, tumor biology 

and the immune system 

and was enabled by the 

inherent flexibility of the NIH 

intramural research program 

to respond quickly to new 

crises. The discoveries of 

NCI researchers in the early 

days of HIV/AIDS were vital 

in transforming HIV infection 

from a fatal diagnosis to the 

manageable condition it is 

for many today. 

Patients with the mysterious 

immune disorder now known 

as AIDS had been arriving 

at the NIH Clinical Center 

since 1981. When the human 

immunodeficiency virus 

(HIV) was identified by Luc 

Montagnier, M.D., at the 

Pasteur Institute in Paris, and 

then shown by NCI’s Robert 

Gallo, M.D., in 1984 to be the 

cause of AIDS, NCI scientists 

were poised to rapidly act on 

the discoveries. 

At the time, there were 

almost no effective antiviral 

drugs for any disease, and 

it was unclear whether 

stopping HIV from replicating 

was feasible or would allow 

patients’ immune systems 

to recover from an infection. 

But NCI’s Samuel Broder, 

M.D., Hiroaki Mitsuya, 

M.D., Ph.D., and Robert 

Yarchoan, M.D., searched for 

compounds that inhibited 

viral growth in the laboratory 

and then immediately 

initiated first-in-human 

trials at the NIH Clinical 

Center to test them in 

patients. NCI’s strong 

industry collaborations 

helped speed patient 

access to the new drugs.

The NCI researchers first 

focused on a viral enzyme 

called reverse transcriptase 

that HIV needs to multiply. 

They developed an assay 

to test the utility of drugs 

against HIV and gathered 

a number of promising 

compounds to test. 

Azidothymidine (AZT), a 

compound first synthesized 

by Jerome Horowitz, Ph.D., 

in 1964 as an anti-cancer 

drug, was among the 

drugs initially tested. 

In a preliminary clinical 

trial done largely in the 

NIH Clinical Center, NCI 

scientists showed that AZT 

could improve the immune 

function of AIDS patients. 

In a randomized trial, it 

was subsequently shown 

to improve survival of AIDS 

patients. In 1987, it became 

the first drug approved by 

THE FIRST 

AIDS DRUGS

18

ccr.cancer.gov

the U.S. FDA for treatment 

of the disease. AZT was 

subsequently shown to 

markedly reduce the 

perinatal transmission 

of HIV.

Because AZT was not 

entirely effective by itself, 

NCI scientists continued 

to develop and test other 

drugs to treat AIDS, including 

the reverse transcriptase 

inhibitors didanosine (ddI) 

and zalcitabine (ddC). These 

became the second and 

third drugs approved by the 

FDA for AIDS. Combining 

AZT with one of these drugs 

improved the effectiveness 

of antiretroviral therapy. 

Unfortunately, patients often 

developed resistance to 

these drugs. As researchers 

learned more about HIV in 

the following years, they 

were able to develop drugs 

that attacked the virus in 

new ways. NCI scientists 

helped map out the structure 

of another essential viral 

enzyme, the HIV protease, 

to guide the design of a new 

class of HIV drugs. When 

combined with reverse 

transcriptase inhibitors, 

protease inhibitors, 

developed in the mid-1990s, 

dramatically suppressed 

replication of the virus, often 

reducing it to undetectable 

levels. 

The number of AIDSrelated deaths in 

the U.S., which 

exceeded 40,000 

in 1995, declined 

rapidly after the 

introduction of 

this combination 

therapy, called 

highly active 

antiretroviral therapy 

(HAART). HAART has 

dramatically reduced 

AIDS mortality and 

transmission of the virus 

in many parts of the world 

where there has been ready 

access to the medication. 

It has also markedly reduced 

the development of the 

many AIDS-related cancers 

that are associated with 

immunodeficiency. CCR 

scientists have continued 

to study the virus, including 

malignancies such as Kaposi 

sarcoma that are related 

to and influenced by HIV 

infection, and patients living 

with HIV today have even 

more treatment options.

19

Caption: An HIV-infected T cell 

(blue, green) interacts with an 

uninfected cell (brown, purple).

Credit: Donald Bliss, National 

Library of Medicine, NIH; Sriram 

Subramaniam, CCR, NCI, NIH
A major challenge in cancer 

treatment is to precisely 

locate and monitor tumors 

in the body so that the 

tumors can be killed without 

harm to surrounding 

cells. In the past decade, 

multidisciplinary teams of 

CCR researchers have helped 

design breakthrough imaging 

technologies that enable 

a closer understanding of 

where and how tumors grow 

in the human body. One of 

these imaging technologies, 

now known as UroNav, is 

revolutionizing clinicians’ 

ability to accurately diagnose 

and treat prostate cancer. 

The imaging tool UroNav, 

also called MRI/ultrasound 

fusion-guided biopsy, 

overlays an advanced 

magnetic resonance image 

(MRI) of the prostate, done 

at initial diagnosis, with an 

ultrasound image performed 

at the time of biopsy. This 

image fusion technology 

dramatically improves 

the accuracy of locating 

potentially cancerous 

prostate regions that require 

biopsy. Standard multineedle methods of prostate 

cancer biopsy have randomly 

sampled large areas of 

prostate tissue, which 

increases the likelihood 

of false-negative or 

false-positive results. 

MRI/ultrasound fusion 

biopsies permit more precise 

biopsies of abnormalappearing prostate tissue.

A prototype of the new 

method was patented by 

CCR researchers in 2007. 

After extensive testing 

at NIH, the investigators 

combined forces with 

InVivo, a subsidiary of 

Philips Healthcare, to build 

a commercial version of the 

prototype. Now known by 

the name UroNav, the device 

enables three-dimensional, 

real-time visualization of 

prostate tumors during 

biopsy. Released to the 

market in 2013, UroNav, and 

other devices based on the 

same technology, may soon 

replace the current standard 

of care for prostate cancer 

detection and diagnosis. 

A year after its release, 

UroNav was included in U.S. 

News & World Report’s list 

of the top ten most notable 

medical advances in the 

past 25 years. Clinical testing 

is underway to determine 

whether such devices 

may also be used to guide 

localized laser ablation of 

scattered, small prostate 

tumors as an alternative 

to full prostate removal or 

irradiation. 

PRECISE 

CLINICAL 

IMAGING 

OF TUMORS

20

ccr.cancer.gov

Another imaging tool 

developed by CCR 

researchers helps in the 

identification of treatmentresistant tumors. The 

method, called electron 

paramagnetic resonance 

imaging (EPRI), is similar 

to an MRI in that it uses a 

magnetic field to reveal 

properties of atoms. In the 

case of EPRI, however, 

the primary focus is on 

free radicals, which are 

uncharged molecules with a 

free electron. EPRI indirectly 

detects the low oxygen levels 

characteristic of growing 

tumors that occur in a wide 

range of cancers. Tumors 

with inadequate oxygen 

supply, called hypoxic 

tumors, are more resistant to 

radiation and chemotherapy 

and have an increased risk of 

metastasis than tumors with 

normal oxygen levels. 

In 1998, CCR researchers 

used EPRI to create the 

first map of oxygen content 

in tissues and tumors of 

mice. In 2008, the team 

demonstrated that EPRI, 

when used in conjunction 

with MRI, provided 

detailed, three-dimensional 

information about the exact 

location of treatmentresistant tumors in living 

organisms in real time, 

thus creating a roadmap to 

help target treatments to 

these tumors. Today, CCR 

continues to explore EPRI as 

a noninvasive way to detect 

tumor hypoxia in 

patients. 

21

Caption: Peter Pinto, M.D., and 

Peter Choyke, M.D., use UroNav 

to improve accuracy of prostate 

cancer imaging.

Credit: Rhoda Baer
22

NATIONAL ACADEMY 

OF SCIENCE MEMBERS

• Sankar Adhya 

• Susan Gottesman

• Shiv Grewal

• Doug Lowy

• Ira Pastan

• Michael Potter*

• Maxine Singer*

• Lou Staudt 

• Thomas Waldmann

• Sue Wickner

• Carl Wu*

NATIONAL 

ACADEMY OF 

MEDICINE MEMBERS

(formerly the Institute of Medicine)

• Michael Gottesman 

• Richard Hodes

• Elaine Jaffe

• Claude Klee*

• Marston Linehan

• Doug Lowy

• John Niederhuber*

• Ira Pastan

• Steven Rosenberg 

• Thomas Waldmann 

• Sam Wells*

• Carl Wu*

• Stephen Katz*

AMERICAN ACADEMY 

OF ARTS AND 

SCIENCES MEMBERS

• Sankar Adhya 

• Donald Court 

• Michael Gottesman 

• Susan Gottesman 

• Shiv Grewal 

• Claude Klee*

• Michael Lichten 

• Glenn Merlino 

• Stephen O’Brien*

• Ira Pastan 

• Maxine Singer*

• Thomas Waldmann 

• Sue Wickner 

• Carl Wu*

LASKER AWARDS

• Robert C. Gallo (1982,1986)*

• Doug Lowy and John Schiller 

• Michael Potter*

• The NIH Clinical Center

NATIONAL MEDAL 

OF TECHNOLOGY 

AND INNOVATION

• Doug Lowy and John Schiller 

AWARDS 

AND ACCOLADES

* No longer with NCI

23

ccr.cancer.gov

PRESIDENTIAL EARLY 

CAREER AWARDS 

FOR SCIENTISTS 

AND ENGINEERS

• James Gulley 

• Dan Larson

SERVICE TO 

AMERICA MEDALS

• Steven Rosenberg: 2015 Federal 

Employee of the Year 

• Thomas Waldmann: 2009 Career 

Achievement Award 

• Doug Lowy and John Schiller: 2007 

Federal Employees of the Year 

ARTHUR S. 

FLEMMING AWARD 

• Elise Kohn

• Lance Liotta*

• Tom Misteli

• Andre Nussenzweig 

• Carole Parent*

• Shyam Sharan

• Lou Staudt 

NIH DISTINGUISHED 

INVESTIGATORS

• Susan Gottesman

• Shiv Grewal

• Doug Lowy

• Tom Misteli

• Andre Nussenzweig

• Ira Pastan

• Lou Staudt

• John Schiller

• Giorgio Trinchieri

• Thomas Waldmann

• Sue Wickner

• Carl Wu*

FORMER TRAINEES 

WHO WON A NOBEL 

PRIZE

• Robert Lefkowitz*

(mentor: Ira Pastan)

• Daniel Nathans*

(mentor: Michael Potter) 

• Harold Varmus*

(mentor: Ira Pastan) 
25

THE HPV VACCINE

• Yasumoto S, et al. J Virol. 1986;57(2):572-7.

• Kirnbauer R, et al. PNAS. 1992;89(24):12180-12184.

• Kirnbauer R, et al. J Virol. 1993;67(12):6929-36.

• Breitburd F, et al. J Virol. 1995;69(6):3959-63.

• Harro CD, et al. J Natl Cancer Inst. 2001;93(4):

284-292.

• Lowy DR, Schiller JT. J Clin Invest. 2006;116(5):

1167-73.

• Hildesheim A, et al. JAMA. 2007;298(7):743-753.

DISCOVERY OF TGF-β

• Chang EH, et al. Science. 1980;210(4475):1249-51.

• Chang EH, et al. Nature. 1982;297(5866):479-83.

• Cooper CS, et al. Nature. 1984;311(5981):29-33.

• Dean M, et al. Nature. 1985;318(6044):385-8.

• Sporn MB, et al. Science. 1986;233(4763):532-4.

• Velu TJ, et al. Science. 1987;238(4832):1408-10.

• Rubin JS, et al. PNAS. 1989;86(3):802-6.

• Bottaro DP, et al. Science. 1991;251(4995):802-4.

CHROMATIN PIONEERS

• Richard-Foy H, Hager GL. EMBO J. 1987;6(8):

2321-8.

• Archer TK, et al. Science. 1992;255(5051):1573-6.

• Tsukiyama T, et al. Nature. 1994;367:525–532.

• Tsukiyama T, Wu C. Cell. 1995;83:1011–1020.

• Tsukiyama T, et al. Cell. 1995;83:1021–1026.

CYTOKINES AS THERAPY

* included in timeline

• Morgan DA, et al. Science. 1976;193(4257):1007-8.*

• Leonard WJ, et al. Nature. 1984;311:626-31.*

• Rosenberg SA, et al. N Engl J Med.

1988;319(25):1676-80.

• Matsushima K, et al. J Exp Med. 1988;167(6):

1883-93.*

• Burton JD, et al. PNAS. 1994;91(11):4935-9.*

• Johnston JA, et al. Nature. 1994;370(6485):151-3.*

• Kawamura M, et al. PNAS. 1994; 91(14): 6374-8.*

• Sportès C, et al. Clin Cancer Res. 2010;16(2):

727-35.*

• Sportès C, et al. J Exp Med. 2008;205(7):1701-14.

• Conlon KC, et al. J Clin Oncol. 2015;33(1):74-82.*

DEVELOPMENT OF CANCER 

IMMUNOTHERAPY

* included in timeline

• Potter M, Boyce CR. Nature. 1962;193:1086-7.*

• Rosenberg SA, et al. N Engl J Med. 

1985;313(23):1485-92.*

• Chaudhary VK, et al. Nature. 1989;339(6223):

394-7.*

• Onda M, et al. J Immunother. 2001;24(2):144-150.*

• Dudley ME, et al. Science. 2002;98(5594):850-4.

• Phan GQ, et al. PNAS. 2003;100(14):8372-7.*

• Morgan RA, et al. Science. 2006;14(5796):126-9.*

• Kochenderfer JN, et al. Blood. 2010;116(19):

3875-86.*

• Kreitman RJ, et al. J Clin Oncol. 2012;30(15):1822-8.

• Robbins PF, et al. Nat Med. 2013;19(6):747-52.*

• Tran E, et al. Science. 2014;344(6184):641-5.*

GENOMIC CLASSIFICATION 

OF TUMORS

• Zbar B, et al. Nature. 1987;327(6124):721-4.

• Linehan WM, et al. JAMA. 1995;273(7):564-70.

• Emmert-Buck MR, et al. Science.

1996;274(5289):998-1001.

• Schmidt L, et al. Nat Genet. 1997;16(1):68-73.

• Alizadeh AA, et al. Nature. 2000;403(6769):503-11.

• Wright G, et al. PNAS. 2003;100(17):9991-6.

• Dave SS, et al. N Engl J Med. 2004;351(21):2159-69.

CELLULAR IMAGING

• Schröck E, et al. Science. 1996;273(5274):494-7.

• Liyanage M, et al. Nat Genet. 1996;14(3):312-5.

• Phair and Misteli, Nature, 2000;404(6778):604-9.

• Meaburn KJ, et al. J Cell Biol. 2009;187(6):801-1.

• Roukos V, et al. Science. 2013;341(6146):660-4.

• Bartesaghi A, et al. Science. 2015;348(6239):1147-51.

• Meyerson JR, et al. Nature. 2016;537(7621):567-571.

THE FIRST AIDS DRUGS

• Yarchoan R, et al. Lancet. 1987;1:132-5.

• Yarchoan R, et al. Lancet. 1988;1:76-81.

• Yarchoan R, et al. N Engl J Med. 1989;321(11):

726-38.

• Yarchoan R, et al. Science. 1989;245(4916):412-5.

• Miller M, et al. Science. 1989;246(4934):1149-52.

• Jacobo-Molina A, et al. PNAS. 1993;90(13):6320-4.

• Koh Y, et al. Antimicrob Agents Chemother.

2003;47(10):3123-9.

PRECISE CLINICAL 

IMAGING OF TUMORS

• Murugesan R, et al. Magn Reson Med. 

1997;38(3):409-14.

• Kuppusamy P, et al. Cancer Res. 1998;58(7):1562-8.

• Singh AK, et al. BJU Int. 2008;101(7):841-5.

• Hyodo F, et al. J Pharm Pharmacol. 

2008;60(8):1049-60.

• Turkbey B, et al. Cancer Imaging. 2011;11:31-6.

CCR BY THE NUMBERS

• FY 2008-17: New Employee Invention Reports, 

Issued U.S. patents, Active licenses, Active 

Cooperative Research and Development 

Agreements (CRADAs)

• FY 2015-17: Trainees, Clinical trials, New patients, 

New trials opening

SELECTED 

REFERENCES

24

LEFT SIDE FROM 

TOP TO BOTTOM: 

Title: Killer T cells surround a cancer cell

Credit: Alex Ritter, Jennifer Lippincott Schwartz 

and Gillian Griffiths, NIH

Title: Enzyme repairing DNA

Credit: Tom Ellenberger, Washington University 

School of Medicine in St. Louis; Dave Gohara, Saint 

Louis University School of Medicine

Title: Terry Fry, M.D., and patient

Credit: Daniel Soñe

Title: Dendritic cell with HIV

Credit: Donald Bliss, National Library 

of Medicine, NIH

RIGHT SIDE FROM 

TOP TO BOTTOM: 

Title: T lymphocyte

Credit: NIAID, NIH

Title: Researcher in CCR lab

Credit: Rhoda Baer

Title: Human papillomavirus

Credit: Veronica Falconieri, CCR, NCI, NIH

Title: HIV infecting a human cell

Credit: Seth Pincus, Elizabeth Fischer and Austin 

Athman, NIAID, NIH

Title: Improving resolution by cryo-EM

Credit: Veronica Falconieri, Sriram Subramaniam, 

CCR, NCI, NIH

LANDMARKS 

COVER ART CREDITS

CONTRIBUTORS

Brenda Boersma-Maland

Li Gwatkin

Abbie Harrison

Jessica Johnson

Diana Linnekin

Jennifer Michalowski

Michael Miller
26

NIH Publication No. 18-CA-8040

Printed in March 2018

Center for Cancer Research