BRAF-targeted therapy for metastatic melanoma: rationale, clinical activity and safety

Metastatic melanoma is well known for its aggressive clinical behavior and therapeutic resistance. The standard systemic therapy has shown limited clinical activity with no significant survival benefit. Melanoma is a molecularly heterogeneous malignancy. Several key genetic lesions governing melanoma initiation and progression have been identified, the most common being a point mutation in the BRAF proto-oncogene, which is detected in 50–60% of metastatic melanoma. The prevalence of RAF alteration in metastatic melanoma and other human cancer has prompted significant efforts in the development of BRAF targeted therapy. Several BRAF inhibitors have entered clinical trials, and have shown significant responses even in patients with latestage melanoma. In this article, we review the rationale, clinical activity and safety of BRAF targeted therapy for metastatic melanoma.