Understanding the biology of melanoma and therapeutic implications.

From 1976 to 2010, only 2 medications were approved for treating metastatic melanoma. Between 2011 and 2013, 4 agents were approved and other therapies have shown great promise in clinical trials. Fundamental discoveries, such as the identification of oncogenic mutations in most melanomas, the elucidation of the molecular signaling resulting from these mutations, and the revelation that several cell surface molecules serve as regulators of immune activation, have been instrumental in this progress. This article summarizes the molecular pathogenesis of melanoma, describes the current efforts to target oncogene-driven signaling, and presents the rationale for combining immune and molecular targeting.