Chemoprevention: general perspective.
Chemoprevention is the use of natural or synthetic compounds to block, reverse, or prevent the development of invasive cancers. Cellular carcinogenesis forms the biologic basis for the identification of chemopreventives, assessment of their activity, and ultimately the success or failure of a chemopreventive. Chemopreventive agents undergo multistep evaluations to assess efficacy that are similar in concept but vastly different in practice to standard ablative oncologic therapeutics. In vitro assessments of potential anticarcinogenesis efficacy include measurements of an agent's antioxidant activity, induction of phase II metabolizing enzymes and effects upon cellular proliferation and apoptotic control pathways. In vivo efficacy is assessed primarily in rodent models of carcinogenesis that are specific for a given organ target. The role of genetically modified animal models in the in vivo assessment of chemoprevention agents remains unclear. Clinical assessment of chemopreventive agent efficacy consists of a multistep process of identification of an optimal chemopreventive agent (phase 1), demonstration of efficacy in humans through the modulation of reversal of a tissue, biochemical, and molecular surrogates for neoplastic transformation and invasion (phase 2) and cancer risk reduction in large cohort trials (phase 3). Opportunities and future needs include the development of reliable, predictive in vivo models of carcinogenesis, careful exploration of the preventive pharmacology of therapeutic agents being used for non-cancer prevention indications, and the incorporation of genetic risk cohorts to define cancer chemopreventive efficacy.
Shureiqi
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Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0934, USA.
Reddy
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Brenner
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005544:Forecasting; D020022:Genetic Predisposition to Disease; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000517:prevention & control; D010349:Patient Compliance; D018579:Patient Selection; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors; D012449:Safety; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D015415:Biomarkers; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists