Dean E. Brenner, MD

Dr. Brenner discusses the role of chemopreventives, biomarkers, and early detection for cancer prevention.

Increasing epidemiologic data haveemerged to support an associationbetween 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductaseinhibitor (statin) use and theprevention or delay in the developmentof invasive cancer. The inhibitionof HMG-CoA reductase resultsin the depletion of mevalonate, a precursorof cholesterol, but also of geranylgeranylpyrophosphate andfarnesyl pyrophosphate, both ofwhich are critical for the isoprenylationof important cellular signalingproteins. Alterations in function andexpression of these signaling proteins-particularly Ras and Rho-have been implicated in malignanttransformation and proliferation. Furthermore,the epidemiologic data arebeing surpassed by preclinical datasupporting the concept that inhibitionof critical signaling pathways bystatins can lead to increased cell deathand prevent the proliferation of malignantcells.

Of the many novel new cancer therapeutic concepts under development, chemoprevention recognizes that malignancies derive from a long, complex interaction of environmental stress modulated by individual genetic phenotypic expression. As described in depth by Drs. Singh and Lippman in this two-part article, published in last and this month’s issues of oncology, substances with potential chemopreventive activity have been identified from multiple sources. These include: (1) human cancer epidemiology, with an emphasis on dietary assessment, geographic dietary and environmental variation, and differences in cancer incidence among similar regional populations; (2) from mechanistic hypotheses; and (3) clinical observations after treatment of cancer (eg, tamoxifen [Nolvadex] for breast cancer). Drs. Singh and Lippman ably demon-strate the wide variety of sources of potential chemopreventive agents and describe current research studies and outcomes.