Inhibition of BRAF and MEK in BRAF-mutant melanoma

摘要

Developments in the treatment of disseminated melanoma continue apace. In The Lancet, Georgina Long and colleagues1 present long-term follow-up data from a large, multicentre, phase 3 clinical trial of patients with BRAF Val600Glu/Lys mutant melanoma, treated with the BRAF inhibitor dabrafenib plus either a placebo or the MEK inhibitor trametinib. The combination of BRAF and MEK inhibition is designed to inhibit the MAPK pathway vertically, with the hope of preventing or delaying resistance arising from reactivation of MEK–ERK signalling that typically occurs after single-agent BRAF inhibition. Combination of a BRAF and a MEK inhibitor limits therapeutic escape in vitro and in animal models.2 Reactivation of the MAPK pathway is a common BRAF inhibitor resistance mechanism, present in up to 80% of post-relapse specimens.