Impact of BRAF inhibitors on the immune microenvironment in melanoma

CUTINE AM; STUPIRSKI J; PEREZ SAEZ J; RABINOVICH GA; GREMEL G; VEIGAS F; MENDEZ-HUERGO S; MAHMOUD Y; GATTO S; MORALES R; MARAIS R; MARIÑO KV; GIROTTI MR

Congreso; Reunión Conjunta Sociedades de Biociencias; 2017

BRAF is mutated in 50% of melanoma patients. BRAF is a component of the RAS/RAF/MEK/ERK pathway and BRAF or MEK inhibitors increase progression-free and overall survival in BRAF- mutant patients. However, most patients relapse with acquired resistance and ~20% of patients present intrinsic resistance. Preclinical and translational studies have shown that targeting the RAS/BRAF/MEK/ERK pathway has effects on the expression of immunomodulatory pathways. Most patients who develop resistance to targeted therapies derive little benefit from anti-CTLA-4 and anti PD-1 based immunotherapies.