AKT1 and hepatocellular carcinoma: Similarly, in HCC, resistance to sorafenib and other targeted therapies arises through the coordinated rewiring of pathways, such as the PI3K-AKT and JAK-STAT pathways, within a hypoxic, fibroblast-rich microenvironment that fosters epithelial–mesenchymal transition, cancer stemness, and immune escape.