PRKAA1 and neoplasm: Preclinical studies demonstrate that metformin-pretreated CAR-T cells exhibit enhanced tumor infiltration and significantly prolong survival in glioma-bearing mouse models (140).Engineered hypoxia-tolerant CAR-T cells demonstrate potent antitumor activity with minimal toxicity in ovarian cancer models (141) and CRISPR/Cas9-mediated AMPKα1 knockout in lung cancer cells has been shown to generate stable cell lines with markedly reduced proliferation rates (142), both of which suggest potential translational relevance for GBM.