Chemoprevention of melanoma.

The United States is experiencing a surge in the incidence of cutaneous malignant melanoma. Because melanoma is typically refractory to available anticancer therapy, exploration of preventive strategies has become a priority. In this review, the rationale for chemoprevention, a new and potentially powerful approach to controlling melanoma, is discussed. Chemoprevention success is based on the principles that ultraviolet-induced melanoma is a multistep process, and that molecular events and pathways associated with these steps can be targeted. Early studies using genetically engineered mice have begun to identify a number of relevant molecular pathways in melanoma. For example, Ras signaling pathways comprise all melanoma-related alterations in N-Ras, B-RAF, MAPK/ERK, and Rho proteins, and thus provide a host of potential molecular targets for melanoma chemoprevention. Among the available prospects, the statins, which inhibit Ras and Rho, have shown much promise as chemoprevention agents. However, thorough evaluation of chemoprevention candidates will require the identification of surrogate biomarkers for risk and molecular targets for intervention, as well as high-risk groups in which to focus clinical studies. We anticipate that melanoma chemoprevention research will progress in step with advances in genomics, proteomics, and preclinical mouse modeling, and ultimately provide us with powerful weapons in our struggle to control this escalating, often fatal disease.