RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

Abstract

Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling… (More)
DOI: 10.1038/nature10662