Dabrafenib for treatment of BRAF-mutant melanoma

Melanoma has the highest mortality of all the skin cancer subtypes. Historically, chemotherapy and immunologic therapies have yielded only modest results in the treatment of metastatic melanoma. The discovery of prevalent V600 BRAF mutations driving proliferation makes this oncogenic protein an ideal target for therapy. Dabrafenib, a reversible inhibitor of mutant BRAF kinase, improved response rates and median progression-free survival in patients with V600E BRAF-mutant metastatic melanoma, including those with brain metastases. With a well-tolerated toxicity profile, dabrafenib is effective as a monotherapy; however, resistance eventually develops in almost all patients. As a result, current research is exploring the role of combination therapies with dabrafenib to overcome resistance.