Targeted therapy for melanoma: Rational combinatorial approaches

The treatment of melanoma, the most aggressive form of skin cancer, is being revolutionized by the development of personalized targeted therapy approaches. Mutant-selective BRAF inhibitors and MEK inhibitors have demonstrated impressive clinical results in molecularly selected patients. However, emerging understanding of the molecular heterogeneity of this disease and the identification of multiple mechanisms of resistance to targeted therapies strongly support the rationale for combinatorial approaches. In this review, we will discuss the preclinical and clinical studies that are testing leading hypotheses and emerging combinatorial strategies for the future.