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Categories: Melanoma, Targeted Therapy
Ravi K. Amaravadi, MD, and Keith T. Flaherty, MD
Metastatic melanoma remains one of the most treatment-refractory malignancies. Despite decades of clinical trials testing chemotherapy and immunotherapy, a standard first-line treatment for metastatic melanoma has not yet been established. This review summarizes recent advances in our understanding of the role of targeted therapies including MAPK signaling inhibitors, VEGF signaling inhibitors, survival kinase inhibitors, and cyclin-dependent kinase inhibitors. An overview of melanoma biology and established targets, followed by a summary of completed and ongoing early-phase clinical trials highlights the failure of the first generation of targeted therapies to improve outcomes as single agents. In contrast, early hints of improved outcomes have been generated by clinical trials testing the combination of sorafenib and chemotherapy. The potential of targeted therapies in combination with chemotherapy or regimens consisting of multiple targeted therapies is explored, as increasing evidence suggests that combination therapeutics could finally impact the outcome of metastatic melanoma.