Combination of RAF and MEK Inhibition for the Treatment of BRAF-Mutated Melanoma: Feedback Is Not Encouraged
Academic Article
Overview
MeSH Major
Antineoplastic Combined Chemotherapy Protocols
MAP Kinase Kinase Kinases
Melanoma
Proto-Oncogene Proteins B-raf
abstract
In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored.