BRAF inhibitors and melanoma.

Selective BRAF inhibitors have recently emerged as a new standard treatment for patients with metastatic melanoma harboring activating BRAF mutations. Inhibition of the MAP kinase pathway and initial evidence of antitumor effects are very reliably observed. However, many patients experience short-lived responses, whereas others are durable. An overall survival benefit has been established for them, BRAF in it, the agents that have advanced furthest in clinical development. Nonetheless, attention has immediately turned to understanding de novo and acquired resistance and effort to develop rational combination therapy that will further improve patient outcomes. Opportunities for combining BRAF inhibitors with other signal transduction inhibitors as well as targeted therapies with distinct mechanisms of action are discussed.