Research ArticleCancer

Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma

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Science Translational Medicine  18 Mar 2015:
Vol. 7, Issue 279, pp. 279ra41
DOI: 10.1126/scitranslmed.aaa4691

Melanoma’s triple threat

Combination therapy is the favored approach to fight drug-resistant cancer. For BRAF-mutated melanoma, combining a BRAF inhibitor and checkpoint inhibitors was hoped to improve the antitumor response; however, an early clinical trial was stopped because of liver toxicity. Hu-Lieskovan et al. test the addition of MEK [MAPK (mitogen-activated protein kinase) kinase] inhibitors to this combination therapy in an effort to potentiate the MAPK inhibition of BRAF inhibitors while concurrently decreasing the toxicity. They show in a mouse model of BRAFV600E-driven melanoma that triple therapy with BRAF and MEK inhibitors together with adoptive cell transfer (ACT) immunotherapy induced complete tumor regression in a manner consistent with immune activation. In addition, replacing ACT with anti-PD1 in the triple therapy had similar results, supporting the testing of MEK and BRAF inhibitions with various immunotherapies in patients with BRAF-mutated melanoma.

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