Cutaneous melanoma: pathogenesis and rationale for chemoprevention

Objective: To critically review aspects of melanoma pathogenesis that lend themselves to a chemoprevention strategy. To discuss potential candidate chemoprevention agents with an emphasis on the lipid lowering drugs, the statins, currently, the most promising agents. Data sources: A retrospective review of the literature. Study, selection: Studies included those relevant to melanoma pathogenesis, to the scientific rationale of chemoprevention, and pertinent epidemiologic, pre-clinical, and clinical studies. The referenced study designs and methodologies varied. Data extraction and synthesis: Data were extracted by two reviewers, and the main results are presented in a quantitative descriptive manner. Conclusion: Melanoma is a preventable disease by altering behavior (sun exposure) among at-risk individuals. There is also considerable evidence to suggest that melanoma development may be prevented or delayed by drugs of sufficiently low toxicity to make clinical trials of chemoprevention feasible and potentially successful. Among potential candidate agents, statins have compelling data for long-term safety and sufficient pre-clinical and clinical evidence for efficacy to justify their evaluation in well-designed trials in high-risk individuals, incorporating intermediate biologic endpoints. (c) 2004 Elsevier Ireland Ltd. All rights reserved.