A variety of approved or pending systemic therapies targeting typical tumor-associated pathways in TME, including vascular endothelial growth factor (VEGF)-dependent angiogenesis, adenosine 5′ monophosphate-activated protein kinase (AMPK), and PI3K/AKT/rapamycin (mTOR) mammalian targets, have a limited role in HCC [50]. This evidence concerns the gene AKT1 and neoplasm.