The National Cancer Program consists of 1) an expanded, intensified, and coordinated cancer research program encompassing the research programs conducted and supported by the institute, and the related research programs of the other national research institutes, including an expanded and intensified research program for the prevention of cancer caused by occupational or environmental exposure to carcinogens, and 2) the other programs and activities of the institute.
The National Cancer Institute also conducts control research for the prevention, detection, diagnosis, and treatment of cancer and for the rehabilitation and continuing care needs of patients respecting cancer. All cancer prevention and control activities focus on reducing cancer incidence, morbidity, and mortality through an orderly sequence of research on interventions and their impact in defined populations to the broad application of the research results through demonstration and education programs.
NCI also supports:
November 9, 1937 --The National Advisory Cancer Council held its first meeting.
November 27, 1937 --The Surgeon General awarded first grants-in-aid on the recommendation of the National Advisory Cancer Council.
January 3, 1938 --The National Advisory Cancer Council recommended approval of first awards for fellowships in cancer research.
August 1940 --The Journal of the National Cancer Institute published its first issue.
July 1, 1946 --The cancer control program was established with appropriations to the states for support of cancer control activities. Staff was organized into six sections: biology, biochemistry, biophysics, chemotherapy, epidemiology, and pathology.
July 1, 1947 --NCI reorganized to provide an expanded program of intramural cancer research, cancer research grants, and cancer control activities.
November 13, 1947 --The Research Grants and Fellowship Branch was established. It became the administrative arm of the Advisory Council.
October 1948 --A grants program to medical, dental, and osteopathic schools was initiated for improvement of training in the field of cancer research, diagnosis, and treatment.
July 2, 1953 --NCI inaugurated a full-scale clinical research program in the new Clinical Center.
April 195 5--The Cancer Chemotherapy National Service Center was established in the institute to coordinate the first national, voluntary, cooperative cancer chemotherapy program.
1957 --The first malignancy (choriocarci-noma) was cured with chemotherapy at NCI.
November 1959 --The Journal of the National Cancer Institute inaugurated a series of occasional publications as Monographs to be used for longer scientific communications.
September 13, 1960 --The NCI director appointed an associate director for grants and training, associate director for field studies, and associate director for collaborative research.
January 12, 1961 --The Laboratory of Viral Oncology was established to investigate the relationship of viruses to human cancer.
April 2, 1962 --An exhibit, "Man Against Cancer," opened in Washington, D.C., to commemorate the 25th anniversary of the institute and inaugurate Cancer Progress Year.
May 7, 1962 --The Acute Leukemia Task Force held its first meeting. It focused the combined efforts and resources of scientists on studies of therapy of the acute leukemia patient, and was the forerunner of other task forces on specific forms of cancer.
October 25, 1962 --The Human Cancer Virus Task Force held its first meeting. The task force, of scientists from NCI and other institutions, stimulated the development of special programs in viral oncology.
1963 --Studies were initiated at NCI in Hodgkin's disease with combination chemotherapy.
December 1964 --The report of the President's Commission on Heart Disease, Cancer, and Stroke was published.
January 11, 1966 --NCI reorganized to coordinate related activities. Areas of three scientific directors were established: etiology, chemotherapy, and a group of discipline-oriented laboratories and branches referred to as general laboratories and clinics. Two associate directors were named for program and for extramural activities.
February 13, 1967 --A cancer research center was established by the institute in Baltimore USPHS Hospital to conduct an integrated program of laboratory and clinical research.
April 27, 1970 --At the request of Senator Ralph W. Yarborough, chairman of the Committee on Labor and Public Welfare, the Senate approved the establishment of the National Panel of Consultants on the Conquest of Cancer.
November 25, 1970 --The national panel of consultants submitted to the Senate committee a report entitled "National Program for the Conquest of Cancer."
October 18, 1971 --President Nixon converted the Army's former biological warfare facilities at Fort Detrick, Md., to house research activities on the causes, treatment and prevention of cancer.
December 23, 1971 --President Nixon signed the National Cancer Act of 1971.
July 27, 1972-- A Bureau-level organization was established for the National Cancer Institute, giving the institute and its components organizational status commensurate with the responsibilities bestowed on it by the National Cancer Act of 1971. Under the reorganization, NCI was composed of the Office of the Director and four divisions: Cancer Biology and Diagnosis; Cancer Cause and Prevention; Cancer Treatment; and Cancer Grants (renamed successively the Division of Cancer Research, Resources and Centers, and later the Division of Extramural Activities).
June 20, 1973-- NCI director Dr. Frank J. Rauscher, Jr., announced that eight institutions were recognized as Comprehensive Cancer Centers to bring results of research as rapidly as possible to a maximum number of people. Additional centers were announced on Nov. 2, 1973, June 13, 1974, Oct. 18, 1974, Apr. 8, 1976, Dec. 30, 1976, July 27, 1978, and Mar. 2, 1979. There are now 20.
September 5, 1973-- The President transmitted to Congress the first annual report of the director of the National Cancer Program, a 5-year strategic plan for the program, and the report of the National Cancer Advisory Board. Preparation and transmittal of the documents were mandated by the National Cancer Act of 1971.
September 10, 1974-- The Division of Cancer Control and Rehabilitation was established to plan, direct, and coordinate an integrated program of cancer control and rehabilitation activities with the goal of identifying, testing, evaluating, demonstrating, communicating, and promoting the widespread use of available and new methods for reducing cancer incidence, morbidity, and mortality.
September 12, 1974-- NCI made its first cancer control awards to state health departments for a 3-year program to screen low-income women for cancer of the uterine cervix. At its peak in 1978, the program had grown to a total of 32 states and territories.
December 17, 1974 --NCI and the National Library of Medicine established CANCERLINE, a jointly developed computerized service to provide scientists across the country with information on cancer research projects and published findings.
December 19, 1974 --The Clinical Cancer Education Program was announced to develop more innovative teaching methods in cancer prevention, diagnosis, treatment, and rehabilitation in schools of medicine, dentistry, osteopathy, and public health; affiliated teaching hospitals; and specialized cancer institutions.
1975 --The Cooperative Minority Biomedical Program, as approved by the National Cancer Advisory Board, represented a cofunding effort by NCI to implement and foster cancer research through the DRR Minority Biomedical Research Support Program and the NIGMS Minority Access to Research Careers Program.
August 5, 1977 --NCI celebrated its 40th anniversary with a ceremony on the NIH campus. Senator Warren G. Magnuson of Washington who, as a member of the House of Representatives, introduced a bill to establish the NCI in 1937, sent a message stating: "Those one and a half million Americans who are alive today--cured of cancer--are ample justification for all that we've appropriated over the last 40 years."
1979 --The first human RNA virus (HTLV-I) was discovered by NCI's Dr. Robert C. Gallo.
July 18, 1979 --NCI and the National Naval Medical Center, Bethesda, Md., signed an agreement to cooperate in a cancer treatment research program.
July 10, 1980 --HHS Secretary Patricia Roberts Harris approved institute-wide reorganization. A newly created Division of Resources, Centers, and Community Activities incorporated functions of the former Division of Cancer Control and Rehabilitation and programs for education, training, construction, cancer centers, and organ site research of the former Division of Cancer Research, Resources, and Centers (DCRRC). Other activities of the DCRRC were incorporated into the new Division of Extramural Activities.
April 27, 1981 --A new Biological Response Modifiers Program was established in the Division of Cancer Treatment to investigate, develop and bring to clinical trials potential therapeutic agents that may alter biological responses that are important in the biology of cancer growth and metastasis.
September 1982-- PDQ, a computerized database on cancer treatment information, became available nationwide via the National Library of Medicine's MEDLARS system.
December 16, 1982 --NCI purchased what is now the R. A. Bloch International Cancer Information Center through generous donations to the NCI Gift Fund. This building houses the Journal of the National Cancer Institute; the Scientific Information Branch, which publishes Cancer Treatment Reports and Cancer Treatment Symposia; the International Cancer Research Data Bank; and PDQ.
July 16, 1983 --NCI launched the Community Clinical Oncology Program (CCOP) to establish a cancer control effort which combines the expertise of community oncologists and the NCI clinical research programs. The CCOP initiative is designed to bring the advantages of clinical research to cancer patients in their own communities.
September 1983 --The Office of International Affairs was reorganized to add a Scientific Information Branch and a Computer Communications Branch. The Scientific Information Branch is composed of a literature research section, cancer treatment reports section, Journal of the National Cancer Institute section, and the international cancer research data bank section.
December 5, 1983 --The name of the Division of Cancer Cause and Prevention was changed to the Division of Cancer Etiology (DCE).
The Division of Resources, Centers and Community Activities was renamed the Division of Cancer Prevention and Control (DCPC) to emphasize the division's roles in cancer prevention and control research.
1984 --A policy statement regarding the relationship of the NCI, the pharmaceutical industry, and NCI-supported cooperative groups was developed. The statement articulates the need for collaboration between the NCI and the pharmaceutical industry in pursuing the joint development of anticancer drugs of mutual interest. It also sets forth guidelines for the handling of issues such as the joint sponsorship of trials, the sharing of information between sponsors, maintaining the confidentiality of certain classes of data, the funding of cooperative groups by drug companies, the review of protocols and the publication of results.
The Comprehensive Minority Biomedical Program, DEA, was established to widen the focus of the minority effort along lines of the programmatic thrusts of the institute, thereby giving it trans-NCI responsibilities.
The Cancer Control Science program was established in DCPC to develop programs in health promotion research and to stimulate widespread application of existing cancer control knowledge. Branches include health promotion sciences, cancer control applications and cancer training.
March 6, 1984 --DHHS Secretary Margaret M. Heckler launched a new cancer prevention awareness program by NCI to inform the public about cancer risks and steps individuals can take to reduce risk.
April 1984 --An NCI scientist, Dr. Robert C. Gallo, reported the isolation of a new group of viruses found in the helper T-cells of patients with AIDS or pre-AIDS symptoms, as well as from healthy individuals at high risk for developing AIDS. These viruses were ultimately named human immunodeficiency virus or HIV. This discovery made the control of blood-product-transmitted AIDS feasible by enabling the development of a simple test for the detection of AIDS-infected blood by blood banks and diagnostic laboratories.
August 1985 --The Cancer Prevention Fellowship Program, one of the first formal postdoctoral research training programs in cancer prevention, began.
November 10, 1986 --The International Cancer Information Center was established in the Office of International Affairs, NCI Office of the Director.
May 1987 --As part of NIH's centennial celebration year, NCI commemorated its 50th anniversary.
October 15, 1987 --The DCPC established the Laboratory for Nutrition and Cancer Research with the basic nutrition science section and the clinical/metabolic human studies section.
October 24, 1987 --The Office of Technology Development was established in the NCI Office of the Director as the institute's focal point for the implementation of pertinent legislation, rules and regulations, and the administration of activities relating to collaborative agreements, inventions, patents, royalties, and associated matters.
October 26, 1987 --The DCT abolished the following branches and/or sections and laboratory: the chromosome structure and function section in the Laboratory of Molecular Pharmacology; the Drug Evaluation Branch and its sections; the drug synthesis section and the acquisition section in the Drug Synthesis and Chemistry Branch; the fermentation section and the plant and animal products section in the Natural Products Branch; the chemical resources section, the analytical and product development section and the clinical products section in the Pharmaceutical Resources Branch; the Extramural Research and Resources Branch; and the Animal Genetics and Production Branch; the sections of the Information Technology Branch; the Laboratory of Experimental Therapeutics and Metabolism and its sections; the sections of the Laboratory of Pharmacology and Experimental Therapeutics.
The DCT changed the name of the Laboratory of Pharmacology and Experimental Therapeutics to the Laboratory of Biochemical Pharmacology. The division also established the Laboratory of Medicinal Chemistry, Pharmacology Branch, Biological Testing Branch, and Grants and Contracts Operations Branch.
1988 --In DCT's Clinical Oncology Program, the Clinical Pharmacology Branch merged with the Medicine Branch.
The International Cancer Information Center established as separate office in the NCI Office of the Director.
January 1988 --NCI journals Cancer Treatment Reports and Journal of the National Cancer Institute were consolidated into a biweekly Journal of the National Cancer Institute.
September 30, 1988 --The first Consortium Cancer Center was established, comprised of three historically black medical schools. Component universities supported by this core grant--Charles R. Drew University of Medicine and Science in Los Angeles, Meharry Medical College in Nashville, and Morehouse School of Medicine in Atlanta--focus their efforts on cancer prevention, control, epidemiology, and clinical trials.
April 1989 --The NCI-initiated mechanism of supplementing research grants to encourage recruitment of minority scientists and science students into extramural research laboratories is published as an NIH-wide extramural program announcement. This initiative will be expanded to cover science students and scientists who are women or persons with disabilities.
May 22, 1989 --NCI scientist Dr. Steven A. Rosenberg conducted the first human gene transfer trial using human tumor-infiltrating lymphocytes to which a foreign gene has been added.
September 14, 1990 --Scientists from NCI and NHLBI conducted the first trial in which a copy of a faulty gene was inserted into white blood cells to reverse the immune deficiency it causes. This was the first human gene therapy trial and adenosine deaminase deficiency was treated.
December 19, 1990 --The institute began its year-long celebration of the 20th anniversary of the National Cancer Act by inaugurating a series of articles in the Journal of the National Cancer Institute. The series described the growth in knowledge that has occured in cancer research since 1971.
January 29, 1991 --The first human gene therapy to treat cancer was started. Patients with melanoma were treated with tumor-infiltrating lymphocytes to which a gene for tumor necrosis factor has been added.
September 24, 1991 --Congress held a special hearing to commemorate the 20th anniversary of the National Cancer Act. Dr. Samuel A. Broder, NCI director, thanked Congress for its "consistent vision, leadership, and commitment to the goal of alleviating the death and suffering caused by cancer in this country."
October 1991 --NCI began its Five-a-Day program, in partnership with the nonprofit group, Produce for Better Health, to encourage Americans to eat at least five fruits and vegetables a day.
December 18, 1992 --Taxol (paclitaxel), an anticancer drug extracted from the bark of the Pacific yew, received approval by the FDA for the treatment of ovarian cancer that has failed other therapy. NCI spearheaded the development of the drug through collaboration with the USDA's Forest Service, the Department of the Interior's Bureau of Land Management, and Bristol-Myers Squibb Company, made possible by the Federal Technology Transfer Act of 1986.
November 1993 --The Prostate, Lung, Colo-rectal, and Ovarian trial, designed to determine whether certain screening tests will reduce the number of deaths from these cancers, began recruiting 148,000 men and women, ages 55-74.
February 1995 --The results of the Community Intervention Trial for Smoking Cessation were completed and published.
1995/1996 --NCI leadership initiated a major reorganization, based on recommendations of the Ad Hoc Working Group of the National Cancer Advisory Board and NCI streamlining work groups and quality improvement teams. Two extramural divisions were created--the Division of Cancer Treatment, Diagnosis and Centers and the Division of Cancer Biology. Two intramural divisions were also created--the Division of Basic Sciences and the Division of Clinical Sciences--and one combined intramural/extramural division--the Division of Cancer Epidemiology and Genetics. The Divisions of Cancer Prevention and Control and Extramural Activities remain a part of the NCI structure, but in the extramural program.
May 30, 1997 --The Breast Cancer Prevention Trial, testing the effectiveness of tamoxifen to prevent the disease, ended its 5-year recruitment. Results are expected in 2-3 years.
March 7, 1928 --Senator M. M. Neely introduced S. 3554, "To authorize the National Academy of Sciences to investigate the means and methods for affording Federal aid in discovering a cure for cancer and for other purposes."
April 23, 1929 --Senator W. J. Harris, Georgia, introduced S. 466, "To authorize the Public Health Service and the National Academy of Sciences jointly to investigate the means and methods for affording Federal aid in discovering a cure for cancer and for other purposes."
May 29, 1929 --Senator W. J. Harris introduced S. 4531, authorizing a survey in connection with the control of cancer and providing "That the Surgeon General of the Public Health Service is authorized and directed to make a general survey in connection with the control of cancer and submit a report thereon to the Congress as soon as practicable, together with his recommendations for necessary Federal legislation."
April 2, 1937 --Senator Homer T. Bone of Washington introduced S. 2067, "Authorizing the Surgeon General of the Public Health Service to control and prevent the spread of the disease of cancer." It authorized an annual appropriation of $1 million.
April 12, 1937 --Congressman Warren G. Magnuson of Washington introduced H.R. 6100, an identical bill to S. 2067.
April 29, 1937 --Congressman Maury Maverick of Texas introduced H.R. 6767, "To promote research in the cause, prevention, and methods of diagnosis and treatment of cancer, to provide better facilities for the diagnosis and treatment of cancer, to establish a National Cancer Center in the Public Health Service, and for other purposes.'' It authorized an appropriation of $2,400,000 for the first year and $1 million annually thereafter. The legal office of PHS had helped draft the bill on the basis of suggestions made by Dr. Dudley Jackson of San Antonio, Tex.
July 8, 1937 --A joint hearing of the Senate and House committees was conducted before a subcommittee on cancer research and a revised bill was written.
July 23, 1937 --The National Cancer Institute Act was passed by Congress.
August 5, 1937 --The National Cancer Institute Act, P.L. 244, 75th Congress, was signed by President Franklin D. Roosevelt, "To provide for, foster, and aid in coordinating research relating to cancer; to establish the National Cancer Institute; and for other purposes." An appropriation of $700,000 for each fiscal year was authorized.
March 28, 1938 --House Joint Resolution 468, 75th Congress, was passed, "To dedicate the month of April in each year to a voluntary national program for the control of cancer."
July 1, 1944 --The Public Health Service Act, P.L. 410, 78th Congress, provided that "The National Cancer Institute shall be a division in the National Institute of Health." The act also revised and consolidated many revisions into a single law. The limit of $700,000 annual appropriation was removed.
August 15, 1950 --Public Law 692, 81st Congress, increased the term of office of National Advisory Cancer Council members from 3 to 4 years and the size of the Council from 6 to 12 members, exclusive of the ex officio members.
December 23, 1971 --President Nixon signed P.L. 92-218-the National Cancer Act of 1971--providing increased authorities and responsibilities for the NCI director; initiating a National Cancer Program; establishing a 3-member President's Cancer Panel and a 23-member National Cancer Advisory Board, the latter replacing the National Advisory Cancer Council; authorizing the establishment of 15 new research, training, and demonstration cancer centers; establishing cancer control programs as necessary for cooperation with state and other health agencies in the diagnosis, prevention, and treatment of cancer; and providing for the collection, analysis, and dissemination of all data useful in the diagnosis, prevention, and treatment of cancer, including the establishment of an international cancer data research bank.
July 23, 1974 --The National Cancer Act Amendments of 1974 (P.L. 93-352) were signed by the President to improve the National Cancer Program and to authorize appropriations for the next three fiscal years. P.L. 93-352 also included provisions for disseminating information on nutrition as related to the therapy or causation of cancer, for trials of cytology test programs for the diagnosis of uterine cancer, and for peer review of grant applications and contract projects. It also established a President's Biomedical Research Panel.
August 1, 1977 --The NCI mandate was extended for 1 year when the President signed the Health Planning and Health Services Research and Statistics Extension Act (P.L. 95-83).
November 9, 1978 --The President signed the Community Mental Health Centers Act (P.L. 95-622) amending the National Cancer Act to emphasize education and demonstration programs in cancer treatment and prevention, and stipulating that NCI devote more resources to prevention, focusing particularly on environmental, dietary and occupational cancer causes.
December 17, 1980 --The Health Programs Extension Act of 1980 (P.L. 96-538) was signed into law, extending NCI authorization for 3 years.
November 20, 1985 --The Health Research Extension Act of 1985 (P.L. 99-158) was signed into law. It affirmed the special authorities of NCI and emphasized the importance of information dissemination to the public.
November 4, 1988 --The Health Research Extension Act of 1988 (P.L. 100-607) was signed into law. The 2-year extension reaffirmed the special authorities of NCI and added information dissemination mandates, as well as a requirement to assess the incorporation of cancer treatments into clinical practice and the extent to which cancer patients receive such treatments. A representative from the Department of Energy was added to the National Cancer Advisory Board as an ex officio member.
June 10, 1993 --The NIH Revitalization Act of 1993, P.L. 103-43, was signed. The act encouraged NCI to expand and intensify its efforts in breast cancer and other women's cancers and authorized increased appropriations. Similar language is included for prostate cancer. The institute is also directed to collaborate with NIEHS, to undertake a case control study to assess biological markers of environmental and other potential risk factors contributing to the incidence of breast cancer in specific counties in the Northeast. In FY 1994 NCI is directed to allocate 7 percent of its appropriation to cancer control, in FY 1995, 9 percent, and in FY 1996, 10 percent.
Dr. Klausner was born in New York City on December 22, 1951. He became the 11th director of NCI on August 1, 1995.
Trained as an internist, he combined patient care and basic research in the early days of his career. He earned his undergraduate degree from Yale University in 1973 and his M.D. degree from Duke Medical School in 1976. He was a fellow in internal medicine at Duke Medical Center in 1976-1977.
From 1979 to 1981, following additional training in internal medicine at Massachusetts General Hospital, Dr. Klausner began his research career at NIH in NCI's Laboratory of Mathematical Biology. He worked at NIADDK from 1981 to 1984, when he became chief of the Cell Biology and Metabolism Branch at NICHD.
He is one of the most frequently cited scientists in the world in cellular and molecular biology. His work elucidated general and novel mechanisms for the regulation of complex genetic networks in human cells. He is a renowned leader in the study of iron metabolism and hematochroma-tosis, a disease of impaired regulation of iron uptake by body tissues, which is associated with subsequent development of cirrhosis and liver cancer. He also illuminated the structure and function of the T-cell antigen receptor, the central molecule of the immune system.
Dr. Klausner is an expert on how certain cell surface receptors enable antigens to activate the immune response, and he has contributed to an understanding of the molecular basis for how the cell recognized abnormal or incompletely synthesized antigens, and retrieves and eliminates them. His studies illuminated novel pathways by which molecules traffic and speak to each other within the cell. Most recently, he has collaborated with NCI scientists to study the VHL gene, a member of a new class of tumor suppressor genes, which play a key role in the development of human kidney cancer.
His research has been recognized with numerous awards and honors, including the Outstanding Investigator Award from the American Federation of Clinical Research and the William Damashek Prize for major discoveries in hematology. He was elected to the National Academy of Sciences in 1993 and the American Academy of Arts and Sciences in 1995.
Dr. Klausner has served on the editorial boards of several scientific journals including Chemistry and Biology, Analytical Chemistry, New Biologist, Cell, the Annual Review of Cell Biology, and the Journal of Cell Biology. He is a past president of the American Society of Clinical Investigation and has been chairman of the National Science Education Standards Projects of the National Academy of Science, overseeing the first comprehensive process to provide a vision of scientific literacy in the American educational system and the criteria required to achieve it. He is the author of a textbook of medical immunology and of a widely use textbook of internal medicine.
The components of this research triad interact. For example, population- or community-based research on the effects of exposure to a potential cancer-causing agent links to the laboratory where an understanding of the agent's effect on the cell can be explored. Through these linkages, NCI-funded research has identified a sexually transmitted papillomavirus as a primary cause of cervical cancer and subsequently explained why only certain viral subtypes are cancer-causing; and NCI-funded research has established the relationship between asbestos and mesotheliomas, between reproductive variables such as late menopause and breast cancer, and between dietary factors and a variety of cancers.
Likewise, community-based research on family clusters of cancers can lead to the isolation of the specific genes responsible for inherited cancer syndromes. The identification of specific genetic pathways in cells studied in the laboratory then can be used to predict the course of a patient's disease and his or her response to therapeutic interventions, or to find ways to detect these cancers very early in their development.
The most remarkable progress in the last 25 years has been in knowledge of cancer biology. Researchers are finally beginning to understand what is required to turn a normal cell into a cancer cell. Cancer arises when a single cell changes so that it divides continuously, released from the controls that constrain the replication of normal cells. This transformation is due to changes in the function and activity of genes--segments of DNA containing the information that directs a cell to make a particular protein product.
Of the 100,000 genes found in the human genome, only the altered activities of a small number of genes are responsible for transforming a normal, well-behaved cell—be it in the breast, brain, blood, colon, prostate or other organ—into a cancer cell. Identifying these “cancer genes” defines the central scientific hunt in cancer biology. Their identification provides an unprecedented window into the nature of cancer. These genes normally function to instruct cells to produce accelerators that drive cells to proliferate, brakes that control proliferation, or mechanisms that underlie the repair of DNA damage or the elimination of damaged cells. Some individuals inherit an altered form of a cancer gene. These individuals carry a very high lifetime risk of developing cancer because fewer subsequent changes in DNA are required to take place in one of the trillions of cells in our bodies to transform that cell into a cancer cell.
DNA changes are the fundamental cause of all cancers. These changes can occur due to chemicals, viruses, radiation, and mistakes made each day in the course of duplicating the 3 billion units in our DNA when a cell divides. DNA, the molecule of life, is very vulnerable to damage, but each cell has the remarkable ability to recognize damage and correct it. The changes in DNA required to produce cancer result from the imbalance between damage and the cell’s ability to repair the damage. When a normal cell recognizes damage to its DNA, it stops the process of growth and division called the cell cycle. A normal cell either repairs the damage or, if it fails, undergoes programmed cell death (apoptosis). In the development of cancer, checkpoint controls are lost and the cell continues to divide, transmitting its damaged DNA to its descendants. It is for this reason that cancer is beginning to be seen as a problem of genetic instability.
No one genetic alteration, however, is enough to make a normal, healthy cell a cancer cell. Rather, an accumulation of changes during the lifetime of a cell in a relatively small number of genes is required. This understanding allows us to begin to define the development and evolution of cancer from predisposition to precancer to cancer. Each cancer is ultimately defined by its particular pattern of altered and normal gene activity. This pattern determines the cancer’s rate of growth, tendency to spread, responsiveness to hormones and therapies, and defines the ability of a person’s immune system to recognize and respond to a cancer. These patterns will define what each cancer is and how many different cancers there are. By defining these molecular patterns, researchers are beginning to be able to describe what distinguishes each cancer from its normal counterpart. Advances in the ability to detect, diagnose, and treat each cancer will most likely be found in these differences.
Research on cancer risk quantifies the risk of developing cancer in various populations and strives to identify the factors responsible for these risks. Research in this area is critical to linking knowledge of biological processes to the detection, management, and ultimately, prevention of cancer. Studying people who are at high risk of cancer is particularly important, because it may be possible to identify more readily the factors influencing risk and to assess means for prevention and risk reduction. Behavioral scientists also contribute to understanding risk by studying how people perceive cancer-related risks and by learning how to motivate health professionals and high-risk persons to practice cancer risk reduction strategies.
Epidemiology is the principal discipline used to study cancer patterns in the population and the determinants of cancer risk. Epidemiologists have uncovered distinct cancer patterns among various population groups. For example, African American men have the highest prostate cancer risk of any group in the world, while men in Asian countries have a relatively low risk. Similarly, women in most Asian countries have the lowest rates of breast cancer, while those in the West have the highest. Interestingly, when Asian women migrate to the United States, their breast cancer risk rises over several generations until it matches that found in U.S. white women. These striking variations among populations have proven particularly useful in targeting further epidemiologic research into the causes of cancer. These studies underlie the commitment of the NCI to address the burden of cancer in all population groups in the United States to assure that all benefit from our research.
The epidemiologic approach has been successful in identifying many factors that increase cancer risk, some of which are environmental and lifestyle-related, while others are part of a person’s genetic makeup. With the exception of a few genetic conditions, however, it is still not possible to predict with any degree of certainty that a person having one or more of these factors will develop cancer. This uncertainty is related to the need for a number of alterations to accumulate in the genetic material (DNA) of a single cell for that cell to be transformed into a malignant state.
The single most important exposure that increases cancer risk is the use of tobacco products, particularly cigarette smoking. Smoking is believed to contribute to more than 30 percent of all cancer deaths. In addition, certain aspects of the diet, particularly diets lacking in fruits and vegetables or high in fats, appear to be important contributors to cancer risk. An excess risk of cancer also has been linked to alcohol consumption, radiation (e.g., ultraviolet- and x-rays), certain occupational exposures (e.g., asbestos), environmental pollution (e.g., arsenic), some pharmaceutical agents (e.g., estrogenic drugs), certain viral infections (e.g., human immunodeficiency virus, and human papilloma virus [HPV]), and hormonal factors. In addition, epidemiology plays a key role in revealing inherited cancer predisposition syndromes, as are seen in women who inherit alterations in the BRCA1 gene.
With recent major advances in molecular biology, a strategy called molecular epidemiology has emerged, combining the strengths of epidemiology with sensitive laboratory probes and providing new insights into genetic susceptibility and gene-environment interactions. This kind of interdisciplinary approach promises to elucidate the risk profiles and biologic mechanisms involved in cancer etiology, making it possible to predict cancer risk with greater certainty.
Ultimately, the purpose of understanding tumor biology and identifying cancer risk is to uncover effective ways to intervene in the cancer process. Important advances in both areas are leading to new strategies to prevent, detect, diagnose, and treat cancer.
Our ability to prevent cancer depends on identifying and removing (or at least reversing the effects of) specific risk factors. Clearly, the most important of these is tobacco use. The NCI has strongly supported recent initiatives to avert the initiation of tobacco use among children and teenagers and continues to develop a variety of approaches to cessation among those already addicted. The effect of dietary modification and administration of preventive agents to forestall the occurrence of cancer in high-risk populations is under study. The testing of tamoxifen as a breast cancer preventive in women at high risk for breast cancer is one approach. It should be quite clear, however, that major improvements in chemoprevention will depend on a better understanding of the fundamental mechanisms of carcinogenesis--the process by which normal cells are induced to become malignant.
Researchers have learned to see inside the body of a living human being with a precision that could not have been anticipated by a previous generation of physicians. Computed tomography, magnetic resonance imaging, and ultrasonography simply did not exist as useful clinical tools 25 years ago. Their development depended on first learning how the body interacts with x-rays, magnetic fields, and sound waves, and then figuring out how to create images from these interactions. These technologies permit doctors to locate internal tumors with unprecedented accuracy and to biopsy internal organs without the need for major surgical procedures. There is every reason to believe that further improvement in their powers of resolution will enhance the ability to detect small tumors even earlier than is possible with currently available method such as x-ray mammography. Invasive procedures, such as colonoscopy and bronchoscopy, are on the verge of giving way to “virtual” procedures involving the imaging of these internal structures without any actual invasion of the body by tubes or scopes.
The diagnosis of cancer depends on the microscopic appearance of tissue samples taken from growths or other suspicious lesions in the body. Advances in biological knowledge have improved our ability to subclassify cancers into accurate categories. For example, a better understanding of normal immune system development and biology has led directly to molecular techniques for classifying, for the first time, immune system tumors (lymphomas). More precise classification of cancers is important because it will lead to more precise prediction of clinical outcome for patients and to the discovery of more effective therapies. The experience with lymphoma serves as a model for what will very likely occur in a variety of malignancies. Tumor diagnosis and classification will be revolutionized in the coming years by application of emerging knowledge in molecular genetics.
The past quarter century has seen major progress in the ability to treat certain cancers. In addition to well-publicized improvements in the cure rates for many uncommon tumors, such as Hodgkin’s disease, certain lymphomas, testicular cancer, and a variety of childhood cancers, adding chemotherapy to surgery and/or radiation has increased the cure rates for patients with breast and colorectal cancer. High-dose chemotherapy with stem-cell rescue is effective in the leukemias and is undergoing definitive testing in breast cancer.
The application of molecular biology to the drug discovery process has ushered in the era of biological therapy by permitting the large-scale production of so-called “recombinant” proteins. Following directly from this approach, the availability of interferon-alpha has markedly improved the outlook for patients with a rare form of leukemia. Both interferon and interleukin-2 provide improved tumor shrinkage for some patients with kidney cancer. The availability of bone-marrow stimulatory factors has enhanced the quality of supportive care by mitigating the toxicity of chemotherapy to the blood elements. Over the past 15 years, the formidable problem of treatment-related nausea and vomiting has been markedly lessened by the development of truly effective drugs that reduce this side effect.
NCI is committed to research to improve the quality of life for those who develop cancer. As treatment becomes increasingly effective in the coming years, the emergence of certain problems associated with surviving cancer will continue to be seen. These are of two general types. The first are the challenges to an optimal quality of life posed by the effects of cancer treatment itself.
Although most acute side effects of treatment are rapidly reversible, some, such as the loss of a body part, have a lasting impact. The widespread use of techniques such as breast reconstruction, conservative surgery, and customized limb prostheses have greatly improved the emotional and functional outlook for survivors of breast and bone cancer. The knowledge, gained in a landmark clinical trial, that chemotherapy followed by radiation treatment is as effective as total removal of the voicebox for cancer of the larynx has made preservation of natural speech possible for many patients with this condition. The recent FDA approval of effective drugs for protecting against the cardiac toxicity of the anthracycline antibiotics and the kidney toxicity of cisplatin can be expected to reduce the overall incidence of two particularly troublesome chronic effects of chemotherapy.
The second general problem is the propensity of many cancer survivors to develop second cancers at the same or other body sites. In some cases, this is a treatment effect; many current therapies that effectively treat the patient’s primary cancer unfortunately also promote the development of second cancers in a small fraction of people who receive them. So, for example, women who have received radiation therapy to the chest for the treatment of Hodgkin’s disease are at increased risk for developing breast cancer; and certain chemotherapy regimens are associated with the late appearance of acute leukemia in some patients who survive for years after the treatment. Sometimes, however, the development of a second cancer stems from influences having nothing to do with the therapy. Patients who survive a first cancer of the lung or oral cavity, for example, have a high incidence of subsequent tumors at those sites, probably because of the long-lasting carcinogenic influences of tobacco. Inherited risk may also play a role. Some breast, ovarian, and colorectal cancer patients have a genetic predisposition to those cancers and are likely to develop other primary cancers. The solution to these persistent problems clearly is to discover more targeted and less toxic treatments and to develop better surveillance and prevention strategies for people whose risk is elevated for reasons unrelated to treatment.
Psychosocial and behavioral research has fundamental contributions to make to all aspects of cancer survivorship, both in improving the quality of life for cancer patients as well as those at increased risk of developing cancer. Psychosocial research investigates how cancer affects quality of life and finds ways to address survivors’ needs so they can meet the everyday demands of life and return to a productive lifestyle. NCI is committed to such research to complement its cancer prevention, detection, and treatment research programs. This research will assume even greater importance as genetic advances pose difficult prevention and treatment choices.
Cancer control research bridges the gap between laboratory, clinical and population-based research, and health care by focusing on how to bring our discoveries to the practice of cancer prevention, detection, treatment, and rehabilitation. Effective application is a challenge well-illustrated by the fact that significant smoking rate reductions have taken over 30 years to achieve since the first Surgeon General’s report that showed conclusively the causal link between smoking and cancer.
The science of cancer control is necessarily multidisciplinary and involves behavioral research, epidemiology, health services research, and communication. A cross-cutting theme is to identify the environmental, genetic, physiological, and psychosocial determinants of health, in order to achieve the adoption of new behaviors that can reduce the risk of cancer or improve the prognosis for persons with cancer.
Behavioral research is central to cancer control. A large proportion of cancer is caused or linked to behaviors such as smoking or diet. Through behavioral research, the behavior of individuals and health care professionals can be modified to include the adoption or promotion of healthy practices, such as smoking cessation, adoption of a low-fat, high-fiber, balanced diet, and practicing cancer screening regimens. The development and rigorous evaluation of smoking cessation interventions is urgently needed to assist the 45 million Americans who currently smoke, particularly those who smoke heavily. Research is under way to integrate effective pharmacotherapies with self-help approaches that address both the addictive and behavioral aspects of smoking. Of equal concern is developing strategies to prevent smoking among adolescents. To this end, behavioral scientists are trying to understand why African American adolescents are avoiding tobacco while white youths have been more resistant to messages about the harms of tobacco.
An important aspect of cancer control research is finding those factors that facilitate adoption of recommended regimens. This requires understanding the population in need. Regimens must be sensitive to the economic, cultural, ethnic and social forces acting upon populations. For example, to increase the adoption of Pap smears, which can prevent needless deaths from cervical cancer, the practices and customs of individuals, their communities, and health care professionals must be understood, and interventions tailored appropriately.
Cancer control research often begins by studying the patterns of cancer in populations through epidemiological studies or through the NCI surveillance system that monitors cancer incidence, mortality, and survival. Evaluating cancer patterns provides insight into who is developing cancer and what factors may have contributed to their disease. Researchers examine not only the changing burden of cancer, but also the public’s and health profession’s knowledge, attitudes, and practices related to cancer prevention, early detection, treatment, and rehabilitation. All of this information is essential for designing and evaluating interventions that may reduce the cancer burden. For example, surveillance data have shown clearly that there are survival differences between African American and white populations. Research is under way to identify the factors underlying these differences.
Effective and widespread communication plays a critical part in applying the knowledge gained in biology, epidemiology, and intervention research. The NCI supports research on cancer communication as well as innovative programs to provide information on cancer to the public and to the Nation’s health professionals. Our scientific journal, the Journal of the National Cancer Institute, is one of the premier cancer journals in the world. Although designed primarily to facilitate communication between scientists and clinicians, the journal is often cited in the popular press and therefore is an important channel for public information. The NCI also supports communications between scientists, physicians, and the public through its nationwide Cancer Information Service (1-800-4-CANCER) and the PDQ computer-based cancer and clinical trials information system. These communication systems provide Americans—patients, the public, and physicians—with the most current information possible on cancer treatments and on effective prevention, early detection, and supportive care technologies.
New challenges for cancer control research abound. The evolving health care system poses the challenge of how to introduce cancer discoveries in these settings, and especially important, to find ways that cancer research can be directly integrated into health care through clinical studies. Developing cost-effective cancer interventions is essential and is an important part of cancer-related health services research. Discoveries in genetics and clinical science pose special challenges for cancer control. For example, with the advent of more precise and individual-specific ways of assessing the risk of developing cancer, researchers are faced with an array of new challenges in living with and understanding risk, and with tailoring prevention, detection, and treatment to individual needs.
Indeed, each research advance brings its own challenges which must be met to realize the promise of research.