Ontology highlight
ABSTRACT:
SUBMITTER: Poulikakos PI
PROVIDER: S-EPMC3266695 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Poulikakos Poulikos I PI Persaud Yogindra Y Janakiraman Manickam M Kong Xiangju X Ng Charles C Moriceau Gatien G Shi Hubing H Atefi Mohammad M Titz Bjoern B Gabay May Tal MT Salton Maayan M Dahlman Kimberly B KB Tadi Madhavi M Wargo Jennifer A JA Flaherty Keith T KT Kelley Mark C MC Misteli Tom T Chapman Paul B PB Sosman Jeffrey A JA Graeber Thomas G TG Ribas Antoni A Lo Roger S RS Rosen Neal N Solit David B DB
Nature 20111123 7377
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 results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E ...[more]