Principles of Targeted Therapy for Melanoma

Targeted BRAF and MEK inhibition has become an appropriate first-line treatment of BRAF-mutant advanced cutaneous melanoma. The authors present an overview of the MAPK pathway as well as the other major pathways implicated in melanoma development. Melanoma brain metastases are a devastating complication of melanoma that can be traced to derangements in cell signaling pathways, and the current evidence for targeted therapy is reviewed. Finally, activating KIT mutations are rarely found to cause melanomas and may provide an actionable target for therapy. The authors review the current evidence for targeted KIT therapy and summarize the ongoing clinical trials.