Old habits die hard: Addiction of BRAF-mutant cancer cells to MAP kinase signaling

Abstract

Dual and triple combination therapies with RAF inhibitors plus other targeted agents have demonstrated promising clinical utility in BRAFV600 -mutant solid tumors. However, despite vertical inhibition at multiple nodes on the MAPK signaling pathway, resistant tumors emerge. Ahronian and colleagues show that in BRAF-mutant colorectal cancer, resistance involves reactivation of RAS/RAF/MEK/ERK signaling and may be overcome by newly emerging ERK inhibitors.