PKM and hepatocellular carcinoma: For example, the activity of PKM2, which is highly upregulated and initiates sorafenib resistance in HCC, is mediated by HIF-1a (Chen J et al., 2018) In contrast, Simvastatin, a medicine to lower lipid level, can overcome sorafenib resistance by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis (Feng J et al., 2020).