111 (PB101) - IK930, a novel TEAD inhibitor, sensitizes KRAS and EGFR mutant tumors to oncogene targeted therapy

Abstract

The Hippo signaling pathway plays a key role in the regulation of cell proliferation, survival, and tissue homeostasis. The transcription co-factors YAP and TAZ, the downstream effectors of this pathway, are phosphorylated by the LATS1/2 kinases in response to a signaling cascade initiated by the MST1/2 (Hippo) kinases. Upon phosphorylation, YAP/TAZ can be sequestered in the cytoplasm or targeted for degradation. In the absence of phosphorylation, YAP and TAZ translocate to the cell nucleus where they interact with members of the TEAD transcription factor family to activate target gene expression.