Remarkably, Cas9-mediated acute Sox9 disruption significantly suppressed both Akt-YAP1 and Akt-NRAS-driven cHCC-CCA development regardless of Dnmt1 delivery, as all Sox9 CKO mice remained healthy at 5 weeks when they were sacrificed for comparison to CWT mice. Here, YAP1 is linked to cholangiocarcinoma.