Novel targeted therapies for the treatment of metastatic melanoma.

The National Comprehensive Cancer Network guidelines for the treatment of stage IV metastatic melanoma state that clinical trials should be the preferred treatment option for these patients; therefore, clinical trials for these patients are the "standard of care." Our greater understanding of the molecular biology behind the development of melanoma has guided much of the translational research in this disease and has led to the development of novel targeted therapies. Specifically, advancement in our knowledge of alterations in signal transduction pathways in melanoma has led to the rapid development of a number of pharmacologic agents that inhibit these pathways. This review will discuss changes in signal transduction pathways involved in melanoma, specifically, activated mitogen-activated protein kinase, activated PI3 kinase, and inactivated p53/Rb pathways. This article will also review new targeted therapy in the context of the molecular biology of melanoma.