GSE64550
shRNA knockdown of YAP1 in HCC364 cells, various drug conditions
Through a genetic screen in BRAF mutant tumor cells, we show that the Hippo pathway effector YAP acts as a parallel survival input to promote resistance to RAF-MEK inhibitor therapy. Our data uncover YAP as a novel mechanism of resistance to RAF-MEK targeted therapy. The findings unveil the synthetic lethality of YAP and RAF-MEK co-suppression as a promising strategy to enhance response and patient survival. Overall design: RNAseq analysis of HCC364 (lung adenocarcinoma) cells in the context of drug treatment with PLX4720 (vemurafenib, a BRAF inhibitor) or Trametinib (a MEK inhibitor) alongside shRNA knockdown of the gene YAP1