The MAP kinase signal transduction pathway: promising therapeutic targets used in the treatment of melanoma.

Inhibition of the MAPK pathway significantly improves response, progression-free survival, disease specific survival, and overall survival for patients with BRAF-mutant, unresectable melanoma. The concurrent administration of BRAF and MEK inhibiting agents improves response rate and outcomes and reduces serious adverse effects, including development of new cutaneous malignancies. Triplet therapy with BRAK/MEK combination and immunotherapy has shown in early results to increase duration of response and may be best used sequentially as opposed to concurrently to avoid treatment limiting toxicities. Current clinical trials will further define these therapies and their impact on treatment of melanoma.