CDK4 and hepatocellular carcinoma: Simultaneously targeting ACTR5/IES6 (by CRISPRi) and CDK6 (by ribociclib, a U.S. Food and Drug Administration–approved CDK4/6 inhibitor also known as LEE011 and KISQALI) (39) synergistically suppressed the HepG2 cell growth (Fig. 5, G and H), highlighting the possible combinatorial targeting of the ACTR5/IES6 and CDK6 axis for advanced HCC treatment (Fig. 5I).