By the late 1970s, it was well known that genes from viruses could rapidly transform normal cells into
cancer cells and that the viruses acquired these genes from the genomes of the animals and birds that they
infected. In 1982, three separate laboratories all cloned the first human cancer-causing gene, called an
oncogene. This discovery was the result of the laborious process of testing increasingly smaller pieces of
DNA from a cancer cell for the ability to cause cancer. Subsequent studies confirmed that the oncogene was a
version of a gene called ras, which had been incorporated into the mouse genome from a mouse virus. The ras
gene in the mouse virus had a single genetic change that caused it to induce uncontrolled growth that
resulted in cancer. This elegant work confirmed what had previously been just a notionthat cancer was a
disease of altered genes. This finding began the era of modern molecular cancer research and treatment.
1
Introduction
Cells are the building blocks of all living things. Normal cells multiply in an orderly way and die when no
longer needed. Cancer can be described as uncontrolled growth of abnormal cells from almost any organ or
tissue within the body. The process that leads to cell death is often blocked in cancer cells. Cancer cells
can invade nearby tissues and spread to other parts of the body. Because it takes so many forms and occurs
in so many parts of the body, cancer should be thought of not as a single disease but as a complex set of
diseases that must be studied from multiple perspectives.
The National Institutes of Healths (NIHs) strategic approach to cancer research focuses on understanding
the causes and mechanisms of cancer; accelerating progress in cancer prevention; improving early detection
and diagnosis; developing effective and efficient treatments; understanding factors that influence cancer
outcomes; improving the quality of cancer care; improving the quality of life for cancer patients,
survivors, and their families; and overcoming cancer health disparities.
NIH also coordinates transdisciplinary translational research designed to realize a vision of personalized
medicine. As this vision evolves, doctors will be able to use detailed information about an individuals
tumor and employ molecular and clinical data to guide the selection of therapies or preventive measures that
are most likely to be safe and effective for that person. Personalized medicine promises to improve quality
of life for cancer survivors, minimize adverse side effects of therapy, and reduce disparities among
populations currently experiencing an excess burden of cancer.
Several examples illustrate the types of research advances and promising new initiatives achieved by NIH
scientists and grantees. For example, Gardasil®, the first vaccine to prevent cervical cancer induced by
human papillomavirus (HPV), has the potential to save over 200,000 womens lives worldwide each year,
including 5,000 U.S. womens lives. In another example, using whole-genome scans, the Cancer Genetic Markers of Susceptibility
project has pinpointed common genetic variants associated with increased risk of
breast and prostate cancers. In addition, the National Cancer Institute (NCI) and the National Institute of
Environmental Health Sciences (NIEHS) have launched the
Breast Cancer and Environment Research Centers
to study the impact of prenatal-to-adult environmental exposures that may predispose a woman to breast cancer.
Cancer research is conducted by a number of NIH Institutes and Centers (ICs); most of the research
investment is committed to NCI programs. NCIs two intramural divisions conduct basic, translational,
clinical, and population research, making fundamental discoveries related to cancer causes and mechanisms,
genetics, and host immunological and other responses to cancer and rapidly translating those findings into
novel preventive and detection methods and therapies. Five NCI extramural divisions support research carried
out at nearly 650 universities, hospitals, cancer centers, specialized networks and research consortia, and
other sites throughout the United States and in more than 20 other countries. In addition, NCI provides
infrastructure to help the greater cancer research community take advantage of the potential benefits of
emerging technologies (e.g., genomics, proteomics, bioinformatics, and molecular imaging).
Cancer research conducted or supported by other NIH ICs is wide ranging and often is coordinated with NCI
programs and granteesfor example, the
Surveillance, Epidemiology, and End Results
(SEER) program (a source of information on cancer incidence and survival
in the United States) and the nationwide network of NCI-funded Comprehensive Cancer Centers. Examples of
cancer research within other ICs include:
- National Institute on Aging (NIA) research on prostate and skin cancers and the biology of aging as
it relates to cancer
- NIEHS research on the effects of biological, chemical, or physical agents on human health
- National Heart, Lung, and Blood Institute (NHLBI) research on blood-related cancers and support for
breast, colorectal, and reproductive cancer as the administrative coordinator of the NIH
Womens Health Initiative
- National Institute of Dental and Craniofacial Research (NIDCR) research on head and neck cancers
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) research on liver,
prostate, kidney, colorectal, and bladder cancers
- National Institute of Allergy and Infectious Diseases (NIAID) technology development in support of
cancer research, diagnosis, and therapy and studies of the role of viruses in cancer
- National Institute of Neurological Disorders and Stroke (NINDS) research on brain, spinal cord, and
pituitary cancers
- National Institute of Nursing Research (NINR) HIV/AIDS and Oncology program
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) research on breast and reproductive
cancers
- National Institute of General Medical Sciences (NIGMS) cancer-related basic biomedical research
- National Institute of Biomedical Imaging and Bioengineering (NIBIB) imaging and bioinformatics
technology development in areas that are vital to cancer research
- National Institute on Drug Abuse (NIDA) research on treatments for tobacco addiction serving as
cancer prevention
Burden of Illness and Related Health Statistics
Because cancer is the second leading cause of death in the United States and the economic cost of cancer in
2005 was estimated at over $200 billion (including $74 billion in direct health care costs and over $135
billion in indirect costs associated with lost productivity due to illness and premature death), cancer
research is a major NIH priority.
2 Although significant progress has been made toward reducing
the burden of cancer in America, cancer remains a leading cause of death, second only to heart diseaseone
of every four deaths is due to cancer.
3,4
The American Cancer Society estimated that, in 2007, there were about 1,444,920 new diagnoses of invasive cancer
and 564,830 Americans died of cancer.
5
Moreover, the World Cancer Report indicates that cancer rates are set to increase at an alarming rate globally
specifically, they could further increase by 50% to 15 million new cases in the year 2020.
One sign of progress is that U.S. death rates for the most common cancers and for all cancers combined have
decreased significantly since 1995.6 However,
the annual number of cancer diagnoses is expected to almost double over the next 50 years, from 1.4 million to 2.6
million. Increasing numbers of Americans are surviving cancer. NIH estimated that, on January 1, 2003, 10.5
million living Americans had a history of invasive cancer.
7
These numbers are likely to increase because of the anticipated growth and
aging of the U.S. population.8
The most common cause of cancer-related death in the United States is lung cancer. The three most common
cancers among men are prostate cancer, lung cancer, and colon cancer. For women, the three most frequently
occurring cancers are breast cancer, lung cancer, and colon cancer.9
Significant disparities in the U.S. burden of cancer have been documented through literature reviews,
program reviews, and ongoing research. These disparities are discussed in the section Minority Health and
Health Disparities later in this chapter.
NIH Funding for Cancer Research
In FYs 2006 and 2007, NIH funding for cancer research was $5.575 billion and $5.643 billion
respectively. The table at the end of this chapter indicates some of the research areas involved in this
investment (see Estimates of Funding for Various Diseases, Conditions, and Research Areas).
Summary of NIH Activities
Across NIH, cancer research activities are focused on two overarching goals: preempting cancer at every
opportunity and ensuring the best outcomes for all. Specific objectives related to these goals include:
Preempting cancer at every opportunity:
- Understanding the causes and mechanisms of cancer
- Accelerating progress in cancer prevention
- Improving early detection and diagnosis
- Developing effective and efficient treatments
Ensuring the best outcomes for all:
- Understanding the factors that influence cancer outcomes
- Improving the quality of cancer care
- Improving quality of life for cancer patients, survivors, and their families
- Overcoming disparities in cancer prevention, diagnosis, treatment, and outcomes
NIH is also exploiting the potential of emerging technologies (e.g., molecular imaging, nanotechnology, and
bioinformatics) in cancer research and care and is building the research infrastructure needed to expand
knowledge and put new insights into practice.
Preempting Cancer at Every Opportunity
Understanding the Causes and Mechanisms of Cancer
Research that improves our understanding of the causes and mechanisms of cancerfrom identifying novel risk
factors to elucidating the processes of metastasis (the spread of cancer from the primary tumor site)is
essential to our ability to develop and apply interventions to preempt cancers initiation and progression.
NIHs plan for deciphering the causes and mechanisms of cancer includes studies in molecular epidemiology to
define complex risk factors, research on the tumor macroenvironment and microenvironment, understanding the
role of altered gene expression in cancer progression and exploring the roles of susceptibility genes in
cancer risk and initiation.
A primary challenge for NIH is dissecting the molecular basis of cancer.
The Cancer Genome Atlas
(TCGA) is developing a comprehensive catalogue of the genetic changes that occur in cancers.
The genomic information generated by TCGA could fuel rapid
advances in cancer research and suggest new therapeutic targets. It could also suggest new ways to
categorize tumors, which might allow clinical trials to focus on those patients who are most likely to
respond to specific treatments. The Childhood Cancer Therapeutically Applicable Research to Generate
Effective Treatments (TARGET) initiative identifies and validates therapeutic targets for childhood
cancers beginning with acute lymphoblastic leukemia and neuroblastoma.
Genetic susceptibility to cancer and cancer risk associated with environmental exposures are also important
research topics. Using powerful new technologies to scan the entire human genome, NIH is conducting
genome-wide association studies to identify unsuspected genetic variants associated with cancer risk.
The Cancer Genetic Markers of Susceptibility
(CGEMS) project, for example, is designed to identify genes that increase the risk of breast and prostate cancers.
Similar efforts are directed at cancers of the pancreas, bladder, lung, and other organs. The results of
these genome-wide studies promise to provide novel strategies for cancer detection, prevention, and
treatment.
Another major NIH initiative is the Sister Study,
which is investigating environmental and genetic risk factors for breast cancer. This study involves a cohort of 50,000 sisters
of women who have had breast cancer. These unaffected sisters are being followed over time, with periodic
health updates. The women who develop breast cancer during the follow-up period will be compared with those
who remained healthy to identify factors associated with increased cancer risk. NIH is also supporting a
network of Breast Cancer and Environment Research Centers (
BCERCs) to study the impact of prenatal to adult environmental exposures that may predispose a woman to
breast cancer. One of the goals of the BCERCs is to develop public health messages to educate young girls
and women who are at high risk of breast cancer about the role of specific environmental stressors in breast
cancer and how to reduce exposures to those stressors.
Other research into the causes and mechanisms of cancer has revealed that tumors function like organs,
comprising many interdependent cell types that contribute to tumor development and progression. The
relationship between tumors and their surrounding cellular environment evolves over time, strongly
influencing tumor progression, metastatic potential, and responsiveness to treatment. The
Tumor Microenvironment Network
is a new NIH program focused on expanding our understanding of the role of the microenvironment in which a tumor originates and
the critical role it plays during tumor development, progression, and metastasis.
Furthermore, interest is growing in the scientific community about the relationship between inflammation and
cancer. NIH is actively pursuing research on the linkages between carcinogenesis and alterations in the
microenvironment induced by inflammation. Inflammation is a response to acute tissue damage, whether
resulting from physical injury, infection, exposure to toxins, or other types of trauma. Current research on
inflammation suggests that pro-inflammatory conditions contribute to the development of several types of
cancer, including lung, stomach, and liver cancers, and may lead to new treatment approaches.
Another area of research focus at NIH is the interface between aging and cancer. As part of an interagency
collaborative effort, eight NCI-designated Cancer Centers are conducting studies on the biology of aging and cancer
and addressing questions related to cancer prevention, treatment, and survivorship in older
patients. This research will help provide insights into why cancer occurs more frequently in older people,
whether cancer behaves differently in older adults than in younger people, whether older patients respond
differently to treatment, and how prevention and screening services should be adapted for this population.
Angiogenesis–the growth of new blood vessels–is required at a certain point for tumors to continue to grow
beyond a size at which they begin to need their own blood supply. Thus, blockade of angiogenesis can prevent
tumor growth. The NIH Trans-Institute Angiogenesis Research Program funds promising angiogenesis research. The programs multidisciplinary approach fosters
data exchange and resource sharing among vascular biology and angiogenesis researchers from different
disease disciplines. A number of new angiogenesis inhibitors are currently being developed, including
several in late-stage clinical trials.
Systems biology and systems genetics are also promising new fields of study that will increase our
understanding of the causes and mechanisms of cancer. These disciplines focus on biological and genetic
networks that can be measured, modeled, and manipulated rather than focusing on the individual components.
Because this research requires multidisciplinary teams of experts in biology, medicine, engineering,
mathematics, and computer science, NIH launched the
Integrative Cancer Biology Program
(ICBP) to develop a framework for these activities. The ICBP has funded nine integrative
biology centers around the United States to provide the nucleus for the design and validation of
computational and mathematical models of cancer. Networks of genes can be found and their associations with
cancer tested and quantified, and parallel association studies can be conducted in relevant human
populations.
NIH is expanding its research portfolio related to the basic biology of tumor stem cells
(also referred to as tumor-initiating cells). Tumor stem cells may be
responsible for the recurrence of malignancy in some cancers. These cells are often resistant to standard
chemotherapeutic agents but may contain unique target molecules that may allow their eradication with novel
molecular therapeutics. Progress has been made in identifying tumor stem cells in multiple myeloma, acute
myelogenous leukemia, and breast cancer.
Accelerating Progress in Cancer Prevention
Current research efforts into preventing cancer focus on modifying behaviors that increase risk, mitigating
the influence of genetic and environmental risk factors, and interrupting the cancer process through early
medical intervention. Dramatic developments in technology and a more complete understanding of the causes
and mechanisms of cancer will enable us to provide more effective ways to prevent the disease. Identifying
critical molecular pathways in precancerous lesions will provide new drug targets for preempting cancer.
Transdisciplinary research will provide a more complete understanding of the interplay of molecular,
behavioral, genetic, and other factors that contribute to cancer susceptibility.
A major step forward in our efforts to prevent cancer has been the development of vaccines that target
HPV.
Persistent infection with HPV is recognized as the major cause of cervical
cancer. Gardasil®, a U.S. Food and Drug Administration (FDA)-approved vaccine against HPV types 6, 11, 16,
and 18–the viral types that cause approximately 70 percent of cervical cancers and 90 percent of genital
warts–is now available. Other similar vaccines against HPV types 16 and 18 and/or additional subtypes are in
development. These vaccines have the potential to save thousands of womens lives annually in the United
States and several hundred thousand more each year worldwide. All of these vaccines resulted directly from
epidemiological, basic, and preclinical research discoveries, as well as the development of a prototype HPV
vaccine, by NIH scientists.
Another area of focus in cancer prevention is cancers relationship with diet and obesity. In its
2006-2007 Annual Report,
the Presidents Cancer
Panel cites evidence that as many as one-third of the nearly 600,000 yearly cancer deaths in the United
States can be attributed to unhealthy diets and obesity. In an effort to reduce the cancer incidence,
morbidity, and mortality associated with obesity, low physical activity, and poor diet, NIH has funded the
Transdisciplinary Research on Energetics and Cancer
(TREC) research centers, which foster collaboration among transdisciplinary teams of scientists.
The TREC research centers are studying factors that lead to obesity and the mechanisms by which obesity
increases the risk of cancer. The TREC initiative is connecting with a number of established initiatives in
the area of diet, physical activity, and weight and is integrated with the NIH Obesity Research Task Force
Strategic Plan.
Because most cases of lung cancer are caused by tobacco use and are, therefore, preventable, multiple NIH
Institutes have co-funded seven
Transdisciplinary Tobacco Use Research Centers
(TTURCs), which seek to identify familial, early childhood, and
lifetime psychosocial pathways associated with smoking initiation, use, cessation, and patterns of
dependence. Research on the genetics of addiction, physiological biomarkers, and advanced imaging techniques
should allow the development of individualized and community approaches to the prevention and treatment of
tobacco-related diseases. The TTURC model demonstrates the feasibility and benefits of scientific
collaboration across disciplines and public-private partnerships.
We now know that the environment and behavioral lifestyles can play a critical role in the development of
cancer. In fact, it was this discovery that led to a public health success story in the 20th century–the
reduction in tobacco use and related diseases. By the mid-1950s, the mysterious and alarming epidemic in
lung cancer, a disease that was almost nonexistent in 1900, was linked to smoking behavior. In the last
decade, overall cancer death rates have dropped for the first time in a century, driven largely by the
dramatic reduction in male smoking from 47 percent in the 1960s to less than 23 percent today. About 40
percent of this drop in overall cancer rates has been credited to the dramatic reduction in male smoking and
male lung cancer deaths since 1991 (more than 146,000 fewer deaths during 1991 to 2003 alone). This success
has been due to public-private partnerships and is also a trans-HHS victory, as significant research
investments have been made over the last 50 years by NCI, NHLBI, NIDA, the National Institute on Alcohol
Abuse and Alcoholism (NIAAA), the John E. Fogarty International Center (FIC), the Centers for Disease
Control and Prevention (CDC), and the Agency for Healthcare Research and Quality (AHRQ). Without these
investments, 40 million Americans might still be smoking today, hundreds of thousands of them would have
prematurely of a tobacco-related disease, and billions of dollars would have been spent on their treatment.10
The NIH-supported Community Clinical Oncology Program
(CCOP) provides a network for greater participation in clinical trials on cancer
prevention and treatment. Over the past 23 years, more than 200,000 people have enrolled in clinical trials
involving CCOP investigators and institutions. One example is the Study of Tamoxifen and Raloxifene
(STAR), which compared the drug raloxifene with the drug tamoxifen in
reducing invasive breast cancer in high-risk postmenopausal women. The initial results from STAR indicate
that raloxifene is as effective as tamoxifen with fewer side effects. The FDA Oncology Drug Advisory
Committee has recommended approval of raloxifene for breast cancer prevention.
Improving Early Detection and Diagnosis
Detecting and diagnosing tumors early in the disease process, before the tumor becomes invasive and
metastatic, can dramatically improve a patients odds for successful treatment and survival and prevent a
large proportion of cancer deaths. Therefore, NIH seeks to accelerate the translation of basic research
findings into sophisticated, minimally invasive procedures that harness imaging, genomic, proteomic,
nanotechnology, and other advanced early-detection and diagnostic techniques.
One NIH effort in the area of early detection is the
National Lung Screening Trial
(NLST), which is comparing two ways of detecting lung cancer–spiral computed tomography
(CT) scans and standard chest X-rays. This study aims to answer the important question whether deaths from
lung cancer can be reduced through the use of CT screening. Research has shown that spiral CT is capable of
detecting not only smaller lung abnormalities, but also more lung cancers than chest x-ray. However, most
of the lung abnormalities seen on screening spiral CTs are not cancer. Moreover, it is not known if finding
these lung abnormalities will actually benefit people by lowering deaths from lung cancer. NLST is designed
to scientifically answer the question of which screening test will better reduce lung cancer deaths and make
meaningful recommendations for public policy.
Molecular profiling is an ongoing effort at NIH, from work at the bench to larger initiatives. In the area
of molecular diagnostics, NIH has formed the
Early Detection Research Network
to bring a collaborative approach to the discovery, development, and validation of early-detection
biomarkers for clinical application. Another NIH program, the
Strategic Partnering to Evaluate Cancer Signatures
program, focuses on confirming, evaluating, and refining signatures derived from the
molecular analysis of tumors (i.e., biomarkers detection) to improve patient management and outcomes. In
addition, the Cancer Genome Anatomy Project
(CGAP) focuses on determining the gene expression profiles of normal,
precancerous, and cancerous cells to improve detection, diagnosis, and treatment. The CGAP Web site makes
tools for genomic analysis available to researchers worldwide.
Yet another area of research that holds promise for advancing molecular diagnostics is proteomics–the study
of complex arrays of proteins produced by cells and tissues. The completion of the Human Genome Project in
2003 has been a major catalyst for proteomics research, and NIH has taken a leading role in facilitating the
translation of proteomics from laboratory research to clinical application through its
Clinical Proteomic Technologies Initiative for Cancer.
The overall objective of this initiative is to build the foundation of technologies (assessment,
optimization, and development), data, reagents and reference materials, computational analysis tools, and
the infrastructure needed to systematically advance our understanding of protein biology in cancer and
accelerate basic science research and the development of clinical applications.
The first product of an NIH-funded research project to integrate new technologies into a reliable clinical
protocol to improve oral cancer detection has reached the market. Researchers report success using a
customized optical device that allows dentists to visualize in a completely new way whether a patient might
have a developing oral cancer. Deviations from the natural fluorescence of healthy tissue may indicate the
presence of developing tumor cells. Health care providers can shine a light onto a suspicious sore in the
mouth, look through an attached eyepiece, and check for changes in color. The instrument is an effective aid
in screening and can guide surgeons when removing tissue for biopsies.
Developing Effective and Efficient Treatments
Developing more effective, more efficient, and less toxic cancer treatments is at the heart of the NIH
cancer research agenda. A strong understanding of the fundamental mechanisms leading to cancer development,
progression, and metastasis will dramatically improve our ability to identify key biochemical pathways in
the disease process as targets for treatment. Acceleration of target validation and the development of new
treatment modalities will be possible through recent advances in biomedical science and technology. Rapid
translation from development to delivery will ensure that promising treatments move safely and efficiently
from preclinical investigation through late-stage clinical trials and into clinical practice. NIH is taking
a multipronged approach to developing new therapies for cancer.
One innovative initiative, the
NCI Experimental Therapeutics Program
(NExT), safely shortens the timeline for moving anticancer drugs from the
laboratory to the clinic by combining NIH expertise in drug development with state-of-the art research
facilities. This program takes advantage of new FDA guidelines that allow human trials, referred to as
Phase 0 or Early Phase I trials, to proceed before traditional, expensive, time-consuming drug
development steps have occurred. The first Phase 0 study has been successfully completed, demonstrating that
this new approach can reduce the number of patients required for an early clinical study and shorten the
time necessary to gather critical drug development information.
Another NIH program, the Cancer Imaging Program
(CIP), supports cancer-related basic, translational, and clinical research in imaging sciences. CIP initiatives include the development and
delivery of image-dependent interventions for malignant and premalignant conditions; standardized models for
the design of clinical trials that use imaging technologies; development of emerging imaging technologies,
including nanotechnology, proteomics, and high-throughput screening; and development of imaging methods for
cancer detection and treatment and for monitoring responses to therapy.
In addition, NIHs Radiation Research Program (RRP) evaluates the effectiveness of radiation research
conducted by grantees. The RRP coordinates its activities with other radiation research programs at NIH,
other Federal agencies, and national and international research organizations. Currently, major clinical
trials are evaluating radiation therapy dose escalation, as well as novel combinations of chemotherapy with
concomitant boost radiation therapy, in non-small cell lung cancer (NSCLC).
Marshalling the exquisite specificity of the immune system to selectively target cancer cells without
harming normal cells is another focus of cancer treatment research at NIH. The Cancer Vaccine and Immunotherapy Program
is evaluating therapeutic cancer vaccines aimed at antigens that are unique to or overexpressed by cancer cells. Other approaches under evaluation include
immunotherapy with T lymphocytes that specifically kill cancer cells, monoclonal antibodies and immunotoxins
that target cancer cells, and the use of cytokines that boost the bodys ability to fight cancer. These a
pproaches may be used in combination with conventional treatments for cancer, such as chemotherapy and
radiotherapy.
NIH launched the Comparative Oncology Program (COP)
in an effort to improve the translational research process. Its mission was to provide an integrated mechanism by which
naturally occurring cancers in pet dogs could be used to generate new information about cancer, translate
biological concepts towards clinical application, and bring novel therapeutic options to the management of
human cancers. As part of this effort, COP has established a multi-center collaborative network of
extramural comparative oncology programs that have completed three clinical trials this year and plans to
initiate five additional trials.
Ensuring the Best Outcomes for All
Research on the quality of cancer care is essential to ensuring the best outcomes for all who may be
affected by cancer. Research in this area can include surveillance as well as epidemiological and
cost-effectiveness studies. In addition, quality-of-life research increases our understanding of the impact
of cancer on patients, survivors, and their family members–many of whom are themselves at increased risk for
cancer due to shared cancer-causing genes, life styles, or environmental exposures. Dissemination research
helps ensure that the knowledge gained through NIH-supported research is appropriately and effectively
communicated to health care providers, policymakers, and the public. An additional goal related to ensuring
the best outcomes for all overcoming health disparities in cancer incidence and outcomes is described in a
later section of this chapter (see Minority Health and Health Disparities).
NIH is currently engaged in making cancer a working model for quality-of-care research and the translation
of the findings of this research into practice. To this end, several collaborative projects have been
initiated: (1) an interagency working committee, The Quality of Cancer Care Committee, which has
fostered collaborative projects directly involving the Health Resources and Services Administration, the
Centers for Medicare and Medicaid Services, and the Department of Veterans Affairs; (2) the National Quality
Forum, a major public-private partnership, to identify core measures of cancer care quality; (3) research on
outcomes measurement by the Cancer Outcomes Measurement Working Group and the Cancer Care Outcomes Research and Surveillance Consortium;
(4) studies on improving the quality of cancer communications; and (5) research
to monitor patterns of treatment dissemination and quality of care through Patterns of Care/Quality of Care Studies, the Prostate Cancer Outcomes Study,
and studies
utilizing the SEER-Medicare Database. In addition, the NCI Community Cancer Centers Program (NCCCP) is
researching how best to bring effective cancer treatments to patients in the communities where they live.
The population of cancer patients surviving more than 5 years continues to grow. NIH continues to support
research and education aimed at professionals who deal with cancer patients and survivors. NIH cancer
survivorship research addresses the physical, psychosocial, and economic impacts of cancer diagnosis and its
treatment and the need for interventions to promote positive outcomes in survivors and their families.
Important early findings suggest long latencies for treatment-related effects, highlighting the need for
extended follow up, early identification, and intervention before complications become more serious.
To improve the outcomes of cancer patients, advances in knowledge must be effectively disseminated to the
public and to health care providers. The Cancer Control P.L.A.N.E.T.
Web portal is a collaborative effort aimed at providing access to data and resources that can help
cancer control planners, health educators, program staff, and researchers design, implement, and evaluate
evidence-based cancer control programs. P.L.A.N.E.T. assists local programs with resources that help them
determine cancer risk and the cancer burden within their State and helps States identify potential partners.
P.L.A.N.E.T. also provides online resources for interpreting research findings and recommendations and for
accessing products and guidelines for planning and evaluation.
Infrastructure for Research
NIH places a high priority on technology development (see the section Technology Development in this
chapter) to support both research and the application of research findings to improve health care delivery,
emphasizing the areas of bioinformatics, cancer imaging, proteomics, and nanotechnology. As NIH-supported
scientists begin to apply new discoveries to cancer prevention, early detection, and treatment, it will be
increasingly important to integrate the tools and insights of research, science, and technology as
effectively as possible.
The Cancer
Biomedical Informatics GridTM (caBIGTM) is an important initiative that has been
launched to accelerate research discoveries and improve patient outcomes by supporting the sharing of data
and tools among researchers, physicians, and patients throughout the cancer community. NIH is committed to
bringing caBIGTM into an enterprise model that can be extended and sustained across a broader
community.
Another initiative, the NCI Alliance for Nanotechnology in Cancer,
is a comprehensive endeavor that involves both the public and the private sectors and is
designed to accelerate the application of the best capabilities of nanotechnology to cancer research. This
initiative supports research on novel nanodevices to detect and pinpoint the location of cancer at its
earliest stages, deliver anticancer drugs specifically to malignant cells, and determine in real time
whether these drugs are effective in killing those cells.
Given the global burden of cancer and opportunities to identify new approaches in prevention and treatment
through international collaborative research, NIH is strengthening health research infrastructure and
building global research capacity through the International Tobacco and Health Research and Capacity
Building Program. This program promotes transdisciplinary approaches to reduce the global burden of
tobacco-related illness and is designed to promote international cooperation between U.S. investigators and
scientists in low- and middle-income nations where tobacco consumption is a current or anticipated public
health urgency. Because the overwhelming majority of smokers begin tobacco use before they reach adulthood,
the program emphasizes research on determinants of youth smoking in diverse cultural and economic settings,
as well as effective ways to prevent young people from starting to smoke.
Personalized Medicine
Advances in these critical aspects of cancer research are being synthesized into a vision of a future
approach to health care called personalized medicine, which will enable clinicians to use detailed
molecular and clinical information about an individuals health to guide the selection of cancer therapies
or preventive measures that are most likely to be safe and effective for that person. The NIH vision of
personalized medicine spans the entire cancer continuum, from prevention through survivorship. Investments
in risk assessment, treatment, and infrastructure development have already yielded progress toward reaching
that vision. Potential benefits of personalized medicine include increased understanding of individual risk
factors, earlier detection and more accurate diagnosis of cancer, more effective targeted treatment,
increased likelihood of survival with improved quality of life, and implementation of high-quality,
patient-centered cancer care through improved communication, informatics, and surveillance.
Notable Examples of NIH Activity
Key for Bulleted Items:
|
E = Supported through Extramural research
I = Supported through Intramural research
O = Other (e.g., policy, planning, or communication)
COE = Supported through a congressionally mandated Center of Excellence program
GPRA Goal = Concerns progress tracked under the Government Performance and Results Act
|
|
Initiatives and Major Programs
Clinical Proteomic Technologies Initiative for Cancer: The completion of the Human Genome Project in
2003 has been a major catalyst for proteomics research, and NIH has taken a leading role in facilitating the
translation of proteomics from research to clinical application through its Clinical Proteomic Technologies
Initiative for Cancer. The overall objective of this Initiative is to build the foundation of technologies
(assessment, optimization, and development), data, reagents and reference materials, computational analysis
tools, and the infrastructure needed to systematically advance our understanding of protein biology in
cancer and accelerate discovery research and clinical applications.
- For more information, see http://proteomics.cancer.gov
- This example also appears in Chapter 3: Genomics and Chapter 3: Technology Development.
- (E/I) (NCI)
NCI Alliance for Nanotechnology in Cancer: The NCI Alliance for Nanotechnology in Cancer is a
comprehensive, systematized initiative that encompasses the public and private sectors and is designed to
accelerate the application of the best capabilities of nanotechnology to cancer. The program supports
research on novel nanodevices that may detect and pinpoint the location of cancer at its earliest stages,
deliver anticancer drugs specifically to malignant cells, and determine in real time whether these drugs are
effective in killing malignant cells. Nanotechnology is likely to change the very foundations of cancer
diagnosis, treatment, and prevention.
- For more information, see http://nano.cancer.gov
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Technology Development.
- (I/E) (NCI)
Cancer Imaging Program (CIP): The CIPs mission is to promote and support cancer-related basic,
translational, and clinical research in the imaging sciences. CIP initiatives include (1) development and
delivery of image-dependent interventions for cancer and pre-cancer; (2) development of standardized models
for the design of clinical trials using imaging; (3) development of emerging imaging technologies, including
nanotechnology, proteomics, and high-throughput screening; and (4) development of imaging methods to detect,
treat, and monitor response to therapy.
- For more information, see http://imaging.cancer.gov
- This example also appears in Chapter 3: Technology Development
- (I/E) (NCI)
Clinical Trials Networks: The Clinical Trials Networks are part of the infrastructure that allows
patients and community physicians access to national studies, facilitating the ability to put successful
regimens into practice:
- The Community Clinical Oncology Program (CCOP) is a network for conducting cancer prevention and
treatment clinical trials. In 23 years of CCOPs, more than 200,000 people have enrolled in treatment and
prevention trials. An example is the Study of Tamoxifen and Raloxifene (STAR), which compares the
effectiveness of these two drugs for reducing the incidence of breast cancer in postmenopausal women at
increased risk of the disease. Initial results indicate that raloxifene is as effective as tamoxifen
with fewer side effects. (For more information, visit http://www.cancer.gov/STAR and
http://dcp.cancer.gov/programs-resources/programs/ccop.)
- Cooperative Group Trials consist of researchers, Cancer Centers, and community doctors who
investigate new cancer treatment, prevention, early detection, quality of life, and rehabilitation. They
involve more than 1,700 institutions, thousands of individual investigators, and more than 22,000
patients each year. These trials are testing therapies that demonstrate improvement to overall patient
survival. For example, the Bevacizumab with Platin-Based Chemotherapy study showed that when the
monoclonal antibody bevacizumab
is added to a paclitaxel-carboplatin chemotherapy regimen for patients
with NSCLC, their overall survival, progression-free survival, and response rates significantly
increased. (For more information, visit http://ctep.cancer.gov.)
- The NCI Community Cancer Centers Program (NCCCP) is a 3-year pilot program to test the concept of a
national network of community cancer centers to alleviate inadequate care delivery. NCCCP will develop
and evaluate programs on community-based cancer care and identify ways to facilitate their broader
engagement in cancer research. (For more information, visit http://ncccp.cancer.gov.)
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NCI)
Community Networks Program (CNP): The CNP aims to reduce and eliminate cancer disparities among
racial minorities through community-based research, education, and training. The goals of the program
are to significantly improve access to and utilization of beneficial cancer interventions in communities
with cancer disparities. A total of 25 projects across the United States and in American Samoa were
launched in May 2005 to address cancer disparities among African Americans, American Indians/Alaska
Natives, Hawaiian Natives and other Pacific Islanders, Asians, Hispanics/Latinos, and rural underserved
populations. Ten grantees work in local areas, 10 in regional areas, and 5 in national programs. Visit:
http://crchd.cancer.gov/cnp/overview.html.
- This example also appears in Chapter 2: Minority Health and Health Disparities.
- (E) (NCI)
Genome-Wide Association Studies of Cancer Risk: Beginning with the Cancer Genetic Markers of
Susceptibility (CGEMS) initiative for breast and prostate cancer, NIH has capitalized on its long-term
investment in intramural and extramural consortia by creating strategic partnerships to accelerate knowledge
about the genetic and environmental components of cancer induction and progression. With powerful new
technology capable of scanning the entire human genome, these efforts have recently identified unsuspected
genetic variants associated with increased risk for developing cancers of the prostate, breast, and colon.
Additional scans, either planned or under way, will be directed at cancers of the pancreas, bladder, lung,
and other organs. The results of these genome-wide studies, together with the follow-on studies planned to
narrow the search for causal gene variants, promise to provide novel clinical strategies for early
detection, prevention, and therapy. To expand upon these emerging opportunities, a new Laboratory of
Translational Genomics (LTG) has been established to further characterize genetic regions associated with
cancer susceptibility and to identify gene-gene and gene-environment interactions. The LTG will create
opportunities for collaboration and data sharing to accelerate the translation of genomic findings into
clinical interventions.
NCI Experimental Therapeutics Program (NExT): The NExT program safely shortens the timeline for
taking anticancer drugs from the laboratory to the clinic by combining NIHs expertise in drug development
with state-of-the art research facilities. The program also utilizes new FDA guidelines that allow early
Phase I clinical trials to proceed before certain time-consuming and expensive drug development steps occur.
The first such study passed the initial stage of clinical examination demonstrating that this new type of
trial can reduce the number of patients required for an early clinical study and the time necessary to
gather critical drug development information.
Systems Biology and Systems Genetics: NIH launched the Integrative Cancer Biology Program to focus on networks that can be measured, modeled, and manipulated rather than individual components. Multidisciplinary
teams are critical to integrating the disciplines of biology, medicine, engineering, math, and computer
science (e.g., computational biology). Equally important to our understanding of cancer is systems genetic
research (systems biology and genetics). Networks of genes can be found and their associations tested and
quantified with parallel association studies on relevant human populations.
- For more information, see http://icbp.nci.nih.gov
- This example also appears in Chapter 3: Molecular Biology and Basic Sciences and Chapter 3: Technology Development.
- (E) (NCI)
The Cancer Biomedical Informatics GridTM: The Cancer Biomedical Informatics GridTM
(caBIGTM) initiative has been launched to accelerate research discoveries and improve patient
outcomes by linking researchers, physicians, and patients throughout the cancer community.
date represents a new phase of evolution, as NIH is committed to bringing caBIGTM into an
enterprise model that can be extended and sustained across a broader community.
- For more information, see http://cabig.cancer.gov
- This example also appears in Chapter 3: Technology Development.
- (E/I) (NCI)
The Cancer Genome Anatomy Project (CGAP): The goal of CGAP is to determine the gene expression
profiles of normal, precancer, and cancer cells to improve detection, diagnosis, and treatment for the
patient. The CGAP Web site makes various tools for genomic analysis available to researchers. Through
worldwide collaborations, CGAP seeks to increase its scientific expertise and expand its databases for the
benefit of all cancer researchers.
The Cancer Imaging Program (CIP): The mission of CIP is to promote and support cancer-related
basic, translational and clinical research in imaging sciences. CIP initiatives include: a) development
and delivery of image-dependent interventions for cancer and pre-cancer; b) standardized models for the
design of clinical trials using imaging; c) development of emerging imaging technologies, including
nanotechnology, proteomics, and high-throughput screening; and d) development of imaging methods to detect,
treat and monitor response to therapy.
The NCI Alliance for Nanotechnology in Cancer: This is a comprehensive, systematized initiative
encompassing the public and private sectors, designed to accelerate the application of the best
capabilities of nanotechnology to cancer. The program supports research on novel nanodevices that may
detect and pinpoint the location of cancer at its earliest stages, deliver anticancer drugs specifically to
malignant cells, and determine in real-time if these drugs are effective in killing malignant cells.
Nanotechnology will likely change the very foundations of cancer diagnosis, treatment and prevention.
- For more information, see http://nano.cancer.gov/
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Technology Development.
- (E/I) (NCI)
The Radiation Research Program (RRP): The RRP establishes priorities, allocates resources, and evaluates
the effectiveness of radiation research and coordinates with other Federal radiation research programs. RRP
has established guidelines for studying proton radiation therapy. Major trials are evaluating radiation
dose escalation in NSCLC and novel combinations of chemotherapy with concomitant-boost radiation therapy in patients with NSCLC.
The Tumor Biology and Metastasis Program: The Tumor Biology and Metastasis Program supports research
to delineate the molecular mechanisms and signaling pathways involved in tumor progression, cell migration
and invasion, angiogenesis, lymphangiogenesis, and metastasis. Research indicates that the progression of
cancer depends on the co-evolution of carcinoma cells in their immediate microenvironment. In 2006, NIH
launched the Tumor Microenvironment Network (TMEN) to investigate the composition of the stroma in normal
tissues. The goal of this network is to delineate the mechanisms of tumor-stromal interactions in human
cancer.
- For more information, see http://tmen.nci.nih.gov
- This example also appears in Chapter 3: Molecular Biology and Basic Sciences.
- (E) (NCI)
The NCI Vaccine Program: NCIs vaccine program develops novel vaccines for cancer immunotherapy and
prevention and HIV. The program encourages collaborations, identifies organizational and reagent needs for
the community, and develops the optimal infrastructure for vaccine development and novel clinical trial
approaches. Gardasil®, the first vaccine to prevent cervical cancer induced by HPV, is now
available and can potentially save more than 5,000 U.S. womens lives each year. This FDA-approved vaccine
resulted from basic research performed at NIH that produced a prototype vaccine and the observation that
linked HPV and cervical cancer.
- This example also appears in Chapter 2: Infectious Diseases and Biodefense and Chapter 3: Clinical and Translational Research.
- (E/I) (NCI)
Long-Term Cancer Survivors Research Initiatives: The population of cancer patients surviving more
than 5 years continues to grow across life stages, from children through senior adults. These research
initiatives focus on the physiological and psychosocial effects of treatment, as well as medical
interventions to promote positive outcomes in survivors and their families. Important early findings
suggest long latencies for treatment-related effects, highlighting the need for extended follow up, early
identification, and intervention before complications become more serious. Implications include the length
and quality of survival and the ongoing burden of illness and costs.
International Tobacco and Health Research and Capacity Building Program: Without a significant shift
in worldwide smoking patterns, tobacco is projected to cause roughly 10 million deaths each year by 2025;
70 percent of this increase will occur in developing countries. To address this rising epidemic, NIH
reissued the International Tobacco and Health Research and Capacity Building Program for funding in 2007.
Grantees are generating a solid evidence base that can inform effective tobacco control strategies and
policies. The program focuses on five critical areas: epidemiology and surveillance, susceptibility and
risk for smoking uptake, behavioral and social sciences, effective interventions, and policy-related
research. The program also emphasizes research on determinants of youth smoking in diverse cultural and
economic settings. A central goal of this program is to strengthen capacity in tobacco research in low- and
middle-income nations, which advances the science and permits greater international collaboration.
The Program in HIV/AIDS & Cancer Virology: The mission of the Program in HIV/AIDS & Cancer Virology
is to facilitate and rapidly communicate advances in the discovery, development, and delivery of antiviral
and immunologic approaches for the prevention and treatment of HIV infection, AIDS-related malignancies,
and cancer-associated viral diseases. This includes basic laboratory, translational, and clinical studies
of disease pathogenesis, the development of novel targeted treatment approaches for cancers in HIV-infected
individuals and for HIV infection itself, and drug resistance. Recent advances include a new prophylactic
vaccine for HPV and promising candidates for prophylactic and therapeutic vaccines against HIV infection.
- For more information, see http://ccr.nci.nih.gov
- This example also appears in Chapter 2: Infectious Diseases and Biodefense.
- (E/I) (NCI)
Trans-Institute Angiogenesis Research Program (TARP): TARP encourages and facilitates the study of
angiogenesis, the formation of new blood vessels. A number of common disease conditions are angiogenesis
dependent, including some cancers, macular degeneration, atherosclerosis, diabetic retinopathy, and many
others. Cancers cannot grow beyond a certain size without new blood vessels. According to one estimate,
more than 500 million people could benefit from anti- or pro-angiogenesis treatments in the coming decades.
TARP funds promising angiogenesis research and provides training and workshops to communicate
state-of-the-art preclinical and clinical angiogenesis research. The programs multidisciplinary approach
fosters data exchange and resource sharing among vascular biology and angiogenesis researchers from
different disease disciplines. A number of new angiogenesis inhibitors are currently being developed,
including several in late-stage clinical trials.
The Sister Study: The Sister Study is a major NIH initiative to study environmental and genetic
risk factors for breast cancer in a cohort of 50,000 sisters of women who have had breast cancer. The
asymptomatic women are being followed over time with periodic health updates. The women who develop breast
cancer during the follow-up period will be compared with those who remained healthy to identify factors
associated with increased cancer risk.
Brain Tumor: The NIH Brain Tumor Progress Review Group identified many priorities for the field.
Research on understanding and preventing brain tumor dispersal was one of the groups highest scientific
priorities, and NIH funds a number of projects in this area, many of which were submitted in response to a
Program Announcement with set-aside funds issued in 2004. NIH also funds clinical studies investigating
therapy delivery to the brain and evaluating the safety and tolerability of various therapies, including
immunological therapies, vaccine therapy, monoclonal antibodies, and combination therapies. The Surgical
and Molecular Neuro-Oncology Unit within the NIH Division of Intramural Research investigates basic
mechanisms of brain tumor development and chemotherapy resistance to find new therapeutic strategies,
particularly for malignant gliomas.
Cancer Stem Cells: NIH is expanding its research portfolio related to the basic biology of
tumor-initiating cells (i.e., stem cells) within the hematological and solid-tumor malignancies. Tumor stem
cells are a minor population of cells thought to be capable of reconstituting an entire tumor. This is
extremely important clinically in that these cells may be responsible for the recurrence of malignancy.
Progress has been made in identifying such minority populations of tumor stem cells in both multiple
myeloma and acute myelogenous leukemia. These tumor-initiating cells are resistant to standard
chemotherapeutic agents but may contain stem cell-unique target molecules that may allow their
eradication with novel small molecular therapeutics. Progress in identifying tumor stem cells among solid
tumors has also been made in breast cancer, where the minority of stem cells have been separated and
characterized from the majority of breast cancer cells in the tumor.
Exemplary Current Studies and Projects
Cancer and Inflammation: NIH is actively pursuing research on the relationship between alterations
in the lung microenvironment caused by inflammation and carcinogenesis. Inflammation is a response to acute
tissue damage, whether resulting from physical injury, ischemic injury, infection, exposure to toxins, or
other types of trauma. Current research on inflammation suggests pro-inflammatory conditions such as
chronic pulmonary irritation contribute to the development of lung cancer and may be strongly correlated
with the occurrence of lung cancer in nonsmokers. Ongoing studies are investigating inflammation in
stomach, liver, and other cancers.
Molecular Profiling of Cancer: The underlying cause of each patients disease is typically unique to
the individual. Because each tumor has its own biological properties, molecular profiling provides advanced
analysis and tools to characterize each individuals disease or tumor so that tailored medical strategies
can be given. Several notable examples include:
- The Early Detection Research Network (EDRN) brings together dozens of institutions to help
detect cancer in its earliest stages. EDRN was formed to bring a collaborative approach to the
discovery, development, and validation of early detection markers by accelerating the translation of
biomarker information into clinical applications.
- The Strategic Partnering to Evaluate Cancer Signatures (SPECS) Program establishes strategic
partnerships to bring together interdisciplinary teams to evaluate the clinical utility of molecular
signatures. SPECS focuses on confirming, evaluating, and refining signatures and/or profiles derived
from molecular analysis of tumors (i.e., biomarkers detection) to improve patient management and
outcomes.
The Cancer Genome Atlas (TCGA): TCGA is a comprehensive and coordinated effort to
accelerate our understanding of the molecular basis of cancer through the application of genome
analysis technologies, including large-scale genome sequencing. The goal of TCGA is to develop
a free, rapidly available, publicly accessible, comprehensive catalog, or atlas, of the many
genetic changes that occur in cancers, from chromosome rearrangements to DNA mutations to
epigenetic changes–the chemical modifications of DNA that can turn genes on or off without
altering the DNA sequence. The overarching goal of TCGA is to improve our ability to diagnose,
treat, and prevent cancer.
Patient Navigation Research Program (PNRP): PNRP is an intervention that addresses
barriers to quality standard care by providing individualized assistance to cancer patients and
survivors and their families. The programs aim is to decrease the time between a
cancer-related abnormal finding, definitive diagnosis, and delivery of quality standard cancer
care. PNRP will focus on the four cancers with the greatest disparity in screening and
follow-up care: breast, cervical, prostate, and colorectal cancers. Nine PNRPs reach African
Americans, American Indians, Asians, Hispanics/Latinos, and rural underserved populations.
Advances in Oral Cancer Detection: The first product of a current NIH-funded research
project to integrate new technologies into a reliable clinical protocol to improve oral cancer
detection and survival has reached the market. Researchers report success using a customized
optical device that allows dentists to visualize in a completely new way whether a patient
might have a developing oral cancer. The simple, handheld device emits a cone of light into the
mouth that excites molecules within our cells, causing them to absorb the light energy and
re-emit it as visible fluorescence. When the light is removed, the fluorescence disappears.
Changes in the natural fluorescence of healthy tissue can indicate light-scattering changes
caused by developing tumor cells. Health care providers shine a light onto a suspicious sore in
the mouth, look through an attached eyepiece, and check for changes in color. Normal oral
tissue emits a pale green fluorescence, whereas early tumor cells appear dark green to black.
The instrument is an effective screening adjunct and is useful for helping surgeons determine
how far to extend the surgical borders when removing tissue for biopsies.
Promoting Early Detection of Oral Cancer in African American Men: NIH is developing a
new series of oral cancer education materials specifically for African American men, who have
the highest risk of oral cancer and the lowest 5-year survival rate (only 35.6 percent) of any
other population in the United States. This is the first national-level effort of its kind. The
first piece in the series, Are You at Risk for Oral Cancer? What African American Men Need to
Know,∇ is now being pre-tested in Washington, DC, Chicago, Los Angeles, and Columbia, South
Carolina. The brochure–along with other complimentary education tools, such as fact sheets,
posters, and both print and audio public service announcements–will be distributed to African
American community groups around the country.
- This example also appears in Chapter 2: Minority Health and
Health Disparities and Chapter 3: Health Communication and Information Campaigns and
Clearinghouses.
- (E/I) (NIDCR, NCI)
Research May Lead to Blood Test to Predict Cancer Treatment Response: In 2007, an
estimated 34,000 Americans will be diagnosed with cancer of the oral cavity and pharynx (the
middle part of the throat that includes the soft palate, tonsils, and tongue), and 7,550
Americans will die from it. Surgical treatment for these cancers may result in a loss of the
ability to speak and swallow. In the largest long-term study of its kind, NIH-supported
scientists determined that patients who showed a decline in specific cancer-related proteins
after chemotherapy and radiation are more likely to remain in remission. These patients may not
need to undergo surgery that may rob them of their speech and swallowing abilities. These
findings could help lead to the development of a blood test that enables doctors to detect the
recurrence of throat cancer at an early stage. A blood test that enables doctors to closely
monitor a patients rehabilitation while sparing the patients voice, speech, and swallowing
ability is an excellent example of NIHs predictive, preemptive, and personalized approach to
medicine.
The Dog Genome and Human Cancer: Cancer is the number-one killer of dogs, and studying
the major cancers in dogs provides a remarkably valuable approach for developing a better
understanding of the development of cancer in humans. The clinical presentation, histology, and
biology of many canine cancers very closely parallel those of human malignancies, so
comparative studies of canine and human cancer genetics should be of significant clinical
benefit to both species. Furthermore, information gained from studying the genetic variant
involved in dog size can provide important information for studying cell growth in humans and
has the potential to be a useful tool in cancer research. A 2007 article by NIHs Dr. Elaine
Ostrander and colleagues reported a genetic variant that is a major contributor to small size
in dogs. In the following month, Dr. Ostrander and colleagues published a study reporting that
a mutation in a gene that codes for a muscle protein can increase muscle mass and enhance
racing performance in dogs.
Salivary Gene Transfer and Therapeutics: Gene transfer may be an ideal strategy to boost
salivary production for cancer patients whose salivary glands were damaged during radiation
therapy. Although radiation therapy kills cancerous cells, it frequently also destroys the
acinar (fluid-producing) salivary gland cells that lie within the salivary gland in grapelike
clusters. Patients are unable to produce adequate saliva and suffer a host of long-term
problems such as recurrent oral infections and difficulties with swallowing, speech, and taste.
Unlike acinar cells, ductal cells in the salivary gland (which can be thought of as the stems
on the grapes) often survive irradiation. However, they cannot make or secrete saliva. NIH
scientists used gene transfer techniques to insert an aquaporin protein gene into the ductal
cells; aquaporins are a family of proteins that form pores in cell membranes, through which
fluid can pass. Their insertion plumps up the stems and allows the flow of fluid into the
mouth again. The scientific team has collaboratively and methodically moved this promising idea
through the research process, benefiting greatly from the wealth of scientific expertise on the
NIH campus. This year, FDA approved the first clinical trial of gene transfer into the salivary
glands for cancer patients with dry mouth. Although the outcome of clinical trials is always
hard to predict, the preclinical data have been extremely promising.
- This example also appears in Chapter 3: Clinical and Translational Research.
- (I) (NIDCR)
Cancer.gov in Español: This Spanish-language version of the NCI Web site is designed to
reach the Hispanic-Latino population–the fastest growing online audience in the country–to
communicate the message that cancer can be prevented and treated and to offer information on
all aspects of the disease. The site is specifically tailored for Hispanics and Latinos, and
pages are organized around issues of greatest concern. The site will be updated with
evidence-based approaches and emerging technologies to ensure that accurate, relevant, and
audience-appropriate information is provided. The site demonstrates the commitment to reducing
cancer health disparities by making information readily available to underserved populations.
- For more information, see http://www.cancer.gov/espanol
- This example also appears in Chapter 2: Minority Health and
Health Disparities and Chapter 3: Health Communication and Information Campaigns and
Clearinghouses.
- (E) (NCI)
Accomplishments
A Multidisciplinary Approach to Nicotine Addiction: Nicotine addiction is the number-one
preventable public health threat and has enormous associated morbidity, mortality, and economic
costs. NIH-supported research has generated new knowledge to support the development of more
effective prevention messages and treatment approaches. Several notable examples characterize
NIHs multidisciplinary approach to targeting the best treatment (or combination of treatments)
for nicotine addiction. Genomic studies have recently uncovered a series of genes that are
associated with nicotine addiction and that could provide new targets for medication
development and for the optimization of treatment selection. Pharmacologic studies, critical to
understanding the basis of nicotines mode of action, have recently revealed that its
addictiveness may hinge upon its ability to slowly shut down or desensitize the brains
response to nicotine. A recent imaging study indicated that a part of the brain called the
insula may play an important role in regulating conscious craving. This exciting finding
provides a new target for research into the neurobiology of drug craving and for the
development of potentially more effective smoking cessation and other addiction treatments.
Results of a Phase II clinical trial strongly suggest that a nicotine vaccine, which works by
preventing nicotine from reaching the brain, may be a particularly useful tool for cessation
programs in the not-too-distant future.
Developmental Windows of Vulnerability to Environmental Exposures: The Breast Cancer and
Environment Research Centers (BCERCs) supported by NIH function as a consortium to study the
impact of prenatal to adult environmental exposures that may predispose a woman to breast
cancer. The centers bring together basic scientists, epidemiologists, research translational
units, and community advocates within and across the centers to investigate mammary gland
development in animals and young girls to determine vulnerability to environmental agents that
may influence breast cancer development in adulthood. The overall goals of the BCERC are to
develop public health messages to educate young girls and women who are at high risk of breast
cancer about the role of specific environmental stressors in breast cancer and how to reduce
exposures to those stressors. These public health messages will be based on the integration of
basic biological, toxicological, and epidemiological data.
- For more information, see http://www.bcerc.org
- This example also appears in Chapter 2: Life Stages, Human
Development, and Rehabilitation.
- (E) (NIEHS, NCI) (GPRA Goal)
Clinical Trials Education: The materials in the Clinical Trials Education series
represent a collection of over 20 resources developed to increase awareness and participation
in cancer prevention and treatment clinical trials. These materials include workbooks, a guide
for community outreach, a trainers guide, online courses for health professionals, DVDs, and
slide sets to assist in education programs.
Health Care Delivery Consortia to Facilitate Discovery and Improve Quality of Cancer Care:
NIH supports several research consortia that are designed to enhance understanding of cancer control across the
continuum of prevention, screening, and treatment within the context of health care delivery.
- The most comprehensive of these initiatives, the Cancer Research Network (CRN),
seeks to improve the effectiveness of preventive, curative, and supportive interventions
for major and rare tumors. The CRN consists of the research programs, enrolled populations,
and data systems of 13 health maintenance organizations covering care for more than 9
million enrollees, or 3 percent of the U.S. population. This initiative uses a consortium
of delivery systems to conduct research on cancer prevention, early detection, treatment,
long-term care, and surveillance. Given its large and diverse populations, the CRN is
uniquely positioned to study the quality of cancer care in community-based settings and to
explore rare conditions. Seminal research includes CRN research documenting specific gaps
in implementing effective tobacco cessation services among clinicians, reasons for late
diagnosis of breast and cervical cancers, more rapid uptake in the use of aromatase
inhibitors in comparison with tamoxifen in treatment for breast cancer, and examination of
the role of a number of common drugs and cancer outcomes using its large and automated
pharmaceutical databases.
- In the area of the evaluation of cancer screening in clinical care, the Breast
Cancer Surveillance Consortium (BCSC) is a collaborative network of mammography
registries linked to tumor and/or pathology registries. The network is designed to assess
the delivery and quality of breast cancer screening and related patient outcomes in the
United States. Because of the vast size and continually updated clinical information in
this research initiative, the BCSC is responsible for research that, for the first time,
documented the falling incidence of hormone replacement therapy among screened women;
quantified the extent of difference in the association of breast density with breast cancer
risk among pre- and postmenopausal women; and determined that, although biopsy rates are
twice as high in the United States than in the United Kingdom, cancer detection rates are
very similar in the two countries.
- The Cancer Care and Outcomes Research Surveillance Consortium (CanCORS) was
established to identify how characteristics of patients, providers, and care delivery
systems affect the cancer management and treatment services that patients receive, as well
as the relationship between cancer-related clinical practices and outcomes, including
patient-centered outcomes such as symptom control and quality of life. CanCORS supports
prospective cohort studies on 10,000 patients with newly diagnosed lung or colorectal
cancers across geographically diverse populations and health care systems and examines
issues related to health outcomes, costs, and patient-centered issues such as symptom
control and quality of life.
Childhood Cancer Survivors Study (CCSS): Although survival rates from childhood cancers
are encouraging, researchers have found that these young survivors may particularly suffer from
late effects of treatment. In 2006, CCSS researchers documented serious long-term health issues
in adults after radiation for childhood cancers. These findings will change treatment regimen
guidelines for current childhood cancers and have implications for individuals from the study
who are now adults. The Childrens Oncology Group (COG) has prepared a resource for physicians,
Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult
Cancers.
The Centers for Transdisciplinary Research on Energetics and Cancer (TREC): These
Centers foster collaboration among transdisciplinary teams of scientists to accelerate progress
toward reducing cancer incidence, morbidity, and mortality associated with obesity, low
physical activity, and poor diet. The biology and genetics of the many factors that influence
diet, physical activity, and obesity across the stages of life are applied to behavioral,
sociocultural, and environmental factors, and transdisciplinary training opportunities are
provided for scientists. The TREC initiative is interfacing with a number of established NCI
initiatives in the area of diet, physical activity, and weight and is integrated with the NIH
Obesity Research Task Force Strategic Plan.
Transdisciplinary Tobacco Use Research Centers: Multiple Institutes at NIH are
co-funding seven collaborative, transdisciplinary centers to identify familial, early
childhood, and lifetime psychosocial pathways related to smoking initiation, use, cessation,
and patterns of dependence. Research on genetics of addiction, physiological biomarkers, and
the use of advanced imaging techniques can lead to individualized and community approaches for
tobacco prevention and treatment. This model demonstrates the feasibility and benefits of
scientific collaboration across disciplines and public-private partnerships.
- For more information, see http://dccps.nci.nih.gov/tcrb/tturc
- This example also appears in Chapter 2: Chronic Diseases and
Organ Systems and Chapter 2: Life Stages, Human Development, and Rehabilitation.
- (E) (NCI, NIAAA, NIDA)
Reports of the Clinical Trials Working Group (CTWG) and the Translational Research Working
Group (TRWG): Recognizing the importance of translational and clinical research, two
recently released, major reports of comprehensive evaluations will lead to more rapid progress
in translating important research findings into new, effective interventions. The CTWG and TRWG
were constituted as broad and inclusive panels (memberships comprise experts from academia, the
pharmaceutical industry, advocacy groups, NIH, and other governmental agencies) to review and
evaluate the current portfolio of research in this area and to identify ways to synergize,
integrate, and coordinate efforts.
Patient and Health Professional Education and Outreach: NIH provides comprehensive
cancer information to those at risk and to patients, caregivers, and health care providers.
This information ranges from prevention, through treatment, to end-of-life topics. For example,
clinical sites across the country extensively utilize NIH print and Web-based materials to
support their educational programs. The Cancer Information Service (CIS) effectively
communicates information through a Partnership Program to help reach those with limited access
to health information; an Information Service that provides cancer information by telephone,
TTY, instant messaging, and e-mail; and a Research Program that helps advance health
communication practices.
Surveillance, Epidemiology, and End Results (SEER) Program and Software Analysis Tools:
SEER is an authoritative source of information on cancer incidence and survival in the United
States. Publications such as the Annual Report to the Nation on the Status of Cancer, as well
as interpretation of recent trends in cancer, inform the public, researchers, Federal and
private agencies, and Congress on national cancer rates and trends. SEER is the only
comprehensive source of U.S. population-based information that includes stage of cancer at the
time of diagnosis, patient survival, and treatment. Linkage with Medicare and other Federal
databases yields information sources that are used routinely to answer major questions on
quality, cost, and variability of cancer care, as well as differences by racial and ethnic
populations. SEER currently collects and publishes data from approximately 26 percent of the
U.S. population. The team is developing computer applications to unify cancer registration
systems, analyze and disseminate data, and provide limited access to the public file. SEER is
considered the standard for quality among cancer registries around the world.
Cancer Control P.L.A.N.E.T.: The Cancer Control P.L.A.N.E.T. (Plan, Link, Act, Network with
Evidence-Based Tools) Web portal is a collaboration aimed at providing access to data and
resources that can help cancer control planners, health educators, program staff, and
researchers design, implement, and evaluate evidence-based cancer control programs. It assists
local programs with resources that help them determine cancer risk and cancer burden within
their State. It also helps States identify potential partners and provides online resources for
interpreting research findings and recommendations and accessing products and guidelines for
planning and evaluation.
The Minority Institution/Cancer Center Partnership (MI/CCP): The MI/CCP provides support
for Minority-Serving Institutions (MSI) to partner with Cancer Centers. MI/CCP goals include:
(1) increasing the participation of MSIs in the Nations cancer research and training
enterprise, (2) enhancing the number of competitive grant funding from minority investigators,
(3) augmenting the research capacity at MSIs, (4) increasing the involvement and effectiveness
of the Cancer Centers in research and training relating to ethnic minorities, and (5)
developing more effective research, outreach, and education programs that will have an impact
on ethnic minority and underserved populations.
- This example also appears in Chapter 2: Minority Health and
Health Disparities.
- (E) (NCI)
Transdisciplinary Tobacco Use Research Centers: Multiple Institutes at NIH are
co-funding seven collaborative, transdisciplinary centers to identify familial, early
childhood, and lifetime psychosocial pathways related to smoking initiation, use, cessation,
and patterns of dependence. Research on genetics of addiction, physiological biomarkers, and
the use of advanced imaging techniques can lead to individualized and community approaches for
tobacco prevention and treatment. This model demonstrates the feasibility and benefits of
scientific collaboration across disciplines and public-private partnerships.
- For more information, see http://dccps.nci.nih.gov/tcrb/tturc
- This example also appears in Chapter 2: Chronic Diseases and
Organ Systems and Chapter 2: Life Stages, Human Development, and Rehabilitation.
- (E) (NCI, NIAAA, NIDA)
Databases for Cervical Cancer Research: NIH has developed data analysis and image
recognition tools for studying biomedical images of HPV infection and cervical neoplasia. Image
data include 100,000 cervicographs (high-definition cervical photographs), Pap test, and
histology images. Tools allow the exploration of visual aspects of HPV and cervical cancer for
research, training, and teaching.
Understanding the Interface Between Aging and Cancer: Through a collaborative effort
between NIA and NCI, eight NCI-designated Cancer Centers are developing studies on the biology
of aging and cancer; patterns of care, treatment efficacy, and tolerance; the effects of
comorbidity, prevention, and screening in older persons; and symptom management and palliative
care in older patients. This research will help gain insights into why cancer occurs more
frequently in older people, whether cancer behaves differently in older adults than in younger
people, and how we need to adapt prevention and screening services to reach a greater number of
older people as well as to aid in the development of predictive models for tolerance to
therapy.
NIH Strategic Plans Pertaining to Cancer
National Cancer Institute (NCI)
National Institute of Dental and Craniofacial Research (NIDCR)
National Center for Complementary and Alternative Medicine (NCCAM)
John E. Fogarty International Center (FIC)
Office of AIDS Research (OAR)
Other Trans-NIH Plans
1 For more information, see http://www.nature.com/milestones/milecancer/full/milecancer17.html
2For more information, see http://obf.cancer.gov/financial/attachments/06Factbk.pdf
3For more information, see http://www.cancer.org.
4For more information, see http://www.cdc.gov/nccdphp/burdenbook2004/index.htm
5American Cancer Society, 2005.
6NCI, 2006.
7For more information, see http://seer.cancer.gov/csr/1975_2003
8Edwards BK, et al. Cancer 2002;94:2766-92, PMID: 12173348
9NCI, 2006.
10Thun MJ, Jemal A. Tobacco Control 2006;15:345-7, PMID: 16998161 |