The use of specific chemicals to prevent the development or retard the progression of carcinogenesis--known as chemoprevention--is a rapidly growing area in cancer research. Developed through the integration of strong laboratory and epidemiologic evidence, chemoprevention research has moved successfully into the clinical research setting, with diverse agents being tested for their efficacy in individuals at high risk of developing certain cancers. The public health potential for reducing cancer incidence and mortality through chemical intervention provides a unique and promising opportunity, and continued support of this multidisciplinary approach to cancer prevention remains a high priority for the U.S. National Cancer Institute.

Antineoplastic Agents↗

PubMed1993

Development of breast cancer chemopreventive drugs.

Breast cancer is the second highest cause of cancer mortality (19%) estimated for U.S. women in 1993 and accounts for the highest proportion of new cancer cases (32%) in this population. The rate of documented cases increased during the early 1970s and again in 1980-87, probably due to early mammographic detection. Increased knowledge of personal risk may also have been a consideration; however, 60% of women diagnosed with breast cancer have no known risk factor(s), such as family history, early age at menarche, late age at menopause, nulliparity, late age at first live birth, socioeconomic status, contraceptive use, postmenopausal estrogen replacement, or high fat intake. To prevent cancer, one strategy undertaken by the NCI is cancer chemoprevention, or intervention with chemical agents at the precancer stage to halt or slow the carcinogenic process. An objective of the NCI, DCPC is to develop promising cancer chemopreventive chemical agents as drugs for human use. Briefly, the process begins with identification of potential agents (e.g., pharmaceuticals, natural products, minor dietary constituents) from surveillance and analysis of the literature and from in vitro prescreen assays. Data on both efficacy (i.e., biological activities that either directly or indirectly indicate inhibition of carcinogenesis) and toxicity are gathered these sources. Various criteria are used to select and prioritize agents for entry into the NCI, DCPC preclinical testing program. The program begins with battery of in vitro efficacy screens using both animal and human cells to select agents for further testing; agents positive in these assays are considered for further testing. In the assay used for breast cancer chemoprevention, 7,12-dimethylbenz(a)anthracene (DMBA)-induced mouse mammary organ culture, 64 chemicals have inhibited formation of hyperplastic alveolar-like nodules. A panel of organ-specific animal screening assays are then used to assess efficacy in vivo. Two assays relevant for breast cancer chemoprevention are inhibition of N-methyl-N-nitrosourea- and DMBA-induced rat mammary gland carcinogenesis. Of 89 agents tested, 29 have inhibited cancer incidence, multiplicity, or both in at least one of the mammary assays; 21 agents are currently on test. Highly promising agents are then placed in traditional preclinical toxicity tests performed in two species. Finally, the most promising and least toxic agents enter clinical trials. Phase I clinical trials are designed to investigate human dose-related safety and pharmacokinetics of the drug. Phase II trials are small scale, placebo-controlled studies designed to determine chemopreventive efficacy and optimal dosing regimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Youth tobacco use in the United States--problem, progress, goals, and potential solutions.

BACKGROUND: Efforts to control tobacco use and tobacco-related morbidity and mortality in the United States continue to be generally successful. In the quarter century since the publication of the first Surgeon General's Report on Tobacco and Health, adult smoking rates in the United States have been reduced by nearly 34%. Controlling tobacco use among our nation's youth, however, has not been as successful. Although there was considerable success in reducing adolescent tobacco use in the late 1970s and early 1980s, tobacco use among youth has remained essentially stable for the past decade. METHODS: The health and economic burden of tobacco use, current knowledge about youth tobacco use, and youth-related national tobacco reduction goals for the Year 2000 are reviewed. RESULTS: Analysis of the research of the past two decades clearly indicates that there is no "magic bullet" in existence or in sight for the reduction of tobacco use, either among youth or among adults. This does not mean that opportunities for significant advances through, for example, pharmacological therapies or the broad application of media or policy strategies should not continue to be explored, but that for the moment no single approach appears to work best. Rather, a comprehensive approach that applies multiple prevention and cessation strategies simultaneously appears to be most effective in tobacco use control. CONCLUSIONS: Among youth, the combination of tobacco control strategies that may work best includes those that involve the family, primary care physicians, and other health professionals such as nurses and dentists; programs that are carried out in schools and/or through the media; and societal approaches such as access and advertising restrictions and increased taxes.

Adolescent↗

PubMed1993

NCI cancer prevention and control research.

As the result of a major prevention and control effort, public health measures directed toward reducing smoking are slowly succeeding (1). Of parallel importance, and the focus of this article, is the research evidence that indicates direct and significant correlations between cancer and certain food groups such as vegetables, fruits, and fiber; the specific components in these foods that may influence cancer risk at several sites; and the intervention trials supported by the National Cancer Institute as part of its chemoprevention research program. The latter includes studies of nutrients and other food constituents as well as pharmaceutical agents that may be useful for cancer prevention.

Animals↗

PubMed1993

Cancer prevention research trials.

Explore the source record for details and available documents.

Animals↗

PubMed1993

Research studies on chemoprevention of esophageal cancer at the United States National Cancer Institute.

Explore the source record for details and available documents.

Alcohol Drinking↗

PubMed1993

Expanding horizons in breast and prostate cancer prevention and early detection. The 1992 Samuel C. Harvey Lecture.

Breast cancer and prostate cancer, the most common cancers in American women and men, respectively, are major public health concerns. Investigations into the prevention and early detection of breast and prostate cancer include research on the potential impact of diet, particularly dietary fat, on breast cancer risk; the chemoprevention of breast cancer using tamoxifen and N-(4-hydroxyphenyl)retinamide(4-HPR); the importance of mammography in early detection of breast cancer; the potential of finasteride in preventing or retarding the progression of early-stage prostate cancer; and improved detection of prostate cancer by combining various screening modalities. The importance of transferring information gained though such research to the health care community cannot be overemphasized. Further, it is critical that cancer prevention and detection education be built into the curricula of leading medical and biomedical institutions. Education is key to developing a strong and vigorous cancer prevention and early detection research program.

Antineoplastic Agents↗

PubMed1992

The study of markers of biological effect in cancer prevention research trials.

Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention.

Antineoplastic Agents↗

PubMed1992

Colon cancer overview.

The scope of current prevention research support by the National Cancer Institute includes the clinical assessment of dietary modifications and cancer screening trials, epidemiologic studies, development of new chemopreventive therapies, and the use of advanced molecular biologic technologies to probe the genetic determinants of colorectal adenomas. Colorectal cancer frequently has been associated with high-fat low-fiber diets in epidemiologic and experimental studies. A recently initiated Phase III Dietary Intervention Study of Recurrence of Large Bowel Adenomatous Polyps will investigate the potential benefits of a low-fat high-fiber fruit-and-vegetable-enriched eating pattern to decrease the polyp recurrence rate. The Chemoprevention Program currently is supporting four Phase III controlled clinical intervention trials investigating the cancer-inhibiting effects on colorectal cancer of beta-carotene, piroxicam, calcium, and calcium plus fiber in persons with previous adenomas. A proposed early detection trial will screen for colorectal, prostate, lung, and ovarian cancers. A comparison of incidence and mortality trends indicates progress in colorectal cancer detection and therapy.

Anticarcinogenic Agents↗