Systemic therapies targeting typical tumor-related pathways in the TME, including VEGF-dependent angiogenesis, PI3K/AKT/mammalian target of rapamycin (mTOR), adenosine 5′-monophosphate-activated protein kinase (AMPK), and c-mesenchymal-epithelial transition factor (c-MET), are approved or under clinical trials for several cancer types, but evidence of their therapeutic efficacy in HCC is limited [123]. This evidence concerns the gene MTOR and hepatocellular carcinoma.