The utilization of Palbociclib, an FDA-approved CDK4/6 inhibitor, in HCC cells demonstrated its ability to rescue the SPINK1-induced increases in self-renewal (Supplementary Fig. S6a-b), chemoresistance (Supplementary Fig. S6c-d), and activation of p-RB-E2F2 signaling (Supplementary Fig. S6e). Here, SPINK1 is linked to hepatocellular carcinoma.