An overview of preventive strategies for pancreatic cancer.

Cancer chemoprevention is defined as the use of specific chemical compounds to prevent, inhibit or reverse carcinogenesis. Chemopreventive intervention can occur throughout carcinogenesis. Many specific food components (e.g. calcium, selenium, folic acid) may also be suitable for chemopreventive use. Chemopreventive drugs are usually administered chronically and are expected to have low toxicity. A variety of mechanisms explain the actions of chemopreventive compounds including modification of carcinogen activation and cellular uptake, inhibition of aberrant signal transduction, induction of apoptosis and inhibition of angiogenesis. As our understanding of carcinogenesis has developed, more specific pharmacologic targets are being selected, e.g. retinoid receptors or cyclo-oxygenases. Definitive, large-scale placebo-controlled randomized trials are necessary to determine the clinical efficacy of chemopreventive compounds. Recent examples include the striking effectiveness of tamoxifen in reducing the risk of breast cancer in women at high risk. Conversely, beta carotene increased the risk of lung cancer in those who continued to smoke and/or who were exposed to asbestos. The future development of predictive risk models that take into account gene-environment interactions will be of considerable value in deciding on specific chemopreventive interventions in those at increased risk by virtue of life style or occupational exposures.