Chemoprevention: general perspective

Chemoprevention is the use of natural or synthetic compounds to block, reve rse, or prevent the development of invasive cancers. Cellular carcinogenesi s forms the biologic basis for the identification of chemopreventives, asse ssment of their activity, and ultimately the success or failure of a chemop reventive. Chemopreventive agents undergo multistep evaluations to assess e fficacy that are similar in concept but vastly different in practice to sta ndard ablative oncologic therapeutics. In vitro assessments of potential an ticarcinogenesis efficacy include measurements of an agent's antioxidant ac tivity, induction of phase II metabolizing enzymes and effects upon cellula r proliferation and apoptotic control pathways. In vivo efficacy is assesse d primarily in rodent models of carcinogenesis that are specific for a give n organ target. The role of genetically modified animal models in the in vi vo assessment of chemoprevention agents remains unclear. Clinical assessmen t of chemopreventive agent efficacy consists of a multistep process of iden tification of an optimal chemopreventive agent (phase 1), demonstration of efficacy in humans through the modulation of reversal of a tissue, biochemi cal, and molecular surrogates for neoplastic transformation and invasion (p hase 2) and cancer risk reduction in large cohort trials (phase 3). Opportu nities and future needs include the development of reliable, predictive in vivo models of carcinogenesis. careful exploration of the preventive pharma cology of therapeutic agents being used for non-cancer prevention indicatio ns, and the incorporation of genetic risk cohorts to define cancer chemopre ventive efficacy. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.