CREB1 and liver cancer: Our investigation, utilizing in vitro cytotoxicity analyses, RNA sequencing, and subcutaneous and in situ models of liver cancer, revealed that, compared to untreated CAR-T cells, CAR-T cells treated with an appropriate concentration (10 μM) of metformin in vitro exhibited a superior antitumor effect in vivo by enhancing metabolic fitness via activating ERK/CREB/PGC-1α axis and promoting STAT3 while inhibiting STAT5 phosphorylation (Figure 9).