The limitations of this study are the lack of (1) rigorous investigations of the potential toxicity of RCF + Ixz in the Hep3B xenograft model; (2) testing the RCF + Ixz combination in a more clinically relevant model of HCC; and (3) identification of the specific mechanisms of how (a) XBP1s increases apoptotic cell death in HCC cells but not in non-cancer cells at later times in vitro and in the Hep3B xenograft model and (b) the decrease in PERK levels prevents P-eIF2α to maintain protein synthesis during proteotoxic stress. Here, EIF2A is linked to hepatocellular carcinoma.