A recent study has shown that ADRB2 signaling restrained autophagy through disruption of the Beclin1/VPS34/Atg14 complex in an AKT-dependent manner, causing HIF1α stabilization, reprogramming of glucose metabolism in HCC cells, and sorafenib resistance in DEN-induced HCC mouse models.82 Despite ample evidence that targeted autophagy processes represent potential therapeutic interventions for HCC (Fig. 3), there are many unresolved issues related to autophagy in sorafenib resistance. The gene discussed is ATG14; the disease is hepatocellular carcinoma.