Adaptive Resistance to Dual BRAF/MEK Inhibition in BRAF-Driven Tumors through Autocrine FGFR Pathway Activation.

Victoria E WangJenny Y XueDennie T FrederickYi CaoEva LinCatherine WilsonAnatoly UrismanDavid P CarboneKeith T FlahertyRene BernardsPiro LitoJeff SettlemanFrank McCormick

Published in: Clinical cancer research : an official journal of the American Association for Cancer Research (2019)

Taken together, these results describe a new, adaptive resistance mechanism that is more commonly observed in the context of dual BRAF/MEK blockade as opposed to single-agent treatment and reveal the potential clinical utility of FGFR-targeting agents in combination with BRAF and MEK inhibitors as a promising strategy to forestall resistance in a subset of BRAF-driven cancers.

Keyphrases

metastatic colorectal cancer
wild type
pi k akt
gene expression
risk assessment
cancer therapy
young adults
drug delivery
signaling pathway
cell proliferation
dna methylation