TEAD inhibitor K-975 enhances KRASG12C inhibitor adagrasib-mediated cancer cell proliferation inhibition via dual cell cycle arrest

ABSTRACT: Here we investigate the effect of the dual inhibition, in KRASG12C mutated NSCLC cells, using the KRASG12Ci adagrasib (MRTX849) and the pan-TEAD inhibitor (TEADi) K-975. We show that K-975 enhances adagrasib-induced tumor cell growth inhibition in cancer cells. Mechanistically, we detect a downregulation of MYC and E2F signatures and a downregulation of the G2/M checkpoint regulation, which result in the increase of G1 and the decrease of the G2/M cell cycle phases. These data suggest that the co-inhibition of KRASG12C and YAP1-TEAD leads to a specific switch in the mechanism of cancer cell killing.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Iris Valtingojer 

PROVIDER: PXD039726 | JPOST Repository | Fri May 12 00:00:00 BST 2023

REPOSITORIES: jPOST