All of them were found to trigger EMT and are involved in EGFR phosphorylation and the AKT-ERK signaling cascade.138–140 Blocking these genes may improve sorafenib antitumor responses, providing a rational combination treatment to increase sorafenib efficacy (Table 5).138,141–143 It has been recently shown that cancer stem cells (CSCs) also participate in therapeutic resistance in HCC. This evidence concerns the gene AKT1 and hepatocellular carcinoma.