Chemoprevention of cancer.
Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention.
Szarka
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Division of Population Science, Fox Chase Cancer Center.
Grana
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Engstrom
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PF
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000517:prevention & control; D002118:Calcium / Q000494:pharmacology; D002986:Clinical Trials as Topic; D000518:Eflornithine / Q000494:pharmacology; D004610:Ellagic Acid / Q000494:pharmacology; D005260:Female; D018120:Finasteride / Q000627:therapeutic use; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis / Q000187:drug effects; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000517:prevention & control; D011719:Pyrazines / Q000494:pharmacology; D012643:Selenium / Q000494:pharmacology; D013629:Tamoxifen / Q000627:therapeutic use; D013871:Thiones; D013876:Thiophenes; D014212:Tretinoin / Q000627:therapeutic use; D014801:Vitamin A / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D013629:Tamoxifen; D014801:Vitamin A; D014810:Vitamin E; D004610:Ellagic Acid; D014212:Tretinoin; D018120:Finasteride; C026209:oltipraz; D012643:Selenium; D001205:Ascorbic Acid; D002118:Calcium; D000518:Eflornithine