Article
Mixed lineage kinases activate MEK independently of RAF to mediate resistance to RAF inhibitors.
Nature communications - 22 May 2014
Marusiak Anna A, Edwards Zoe C, Hugo Willy, Trotter Eleanor W, Girotti Maria R, Stephenson Natalie L, Kong Xiangju, Gartside Michael G, Fawdar Shameem, Hudson Andrew, Breitwieser Wolfgang, Hayward Nicholas K, Marais Richard, Lo Roger S, Brognard John
Abstract excerpt
RAF inhibitor therapy yields significant reductions in tumour burden in the majority of V600E-positive melanoma patients; however, resistance occurs within 2-18 months. Here we demonstrate that the mixed lineage kinases (MLK1-4) are MEK kinases that reactivate the MEK/ERK pathway in the presence of RAF inhibitors. Expression of MLK1-4 mediates resistance to RAF inhibitors and promotes survival in V600E-positive...
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