Next generation therapies change the landscape in melanoma.

Melanoma is among the leading causes of years of life lost due to cancer. Current chemotherapy and cytokine-based immunotherapy approaches benefit only a small percentage of patients with advanced disease. However, the recent discovery of mutations in the gene encoding the serine-threonine kinase B-RAF (BRAF) raises the possibility that oncogene-targeted therapy may provide a new point of vulnerability. In parallel, a deeper understanding of the molecular mechanisms underlying antitumor T-cell activation and tolerance has provided a basis for developing therapies targeted against these processes. Results from an early phase trial with a BRAF inhibitor and a phase III trial with a novel agent that activates T cells have radically altered the prospects for improving outcomes for patients with this historically treatment-refractory disease.