The Role of Ferroptosis on the Pathogenesis and Therapy of Hepatocellular Carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and lack of efficient therapies. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumors, such as HCC. Ferroptosis has been quickly gaining attention in the field of liver diseases, as liver is predisposed to oxidative injury and generally. Emerging evidence supports the notion that dysregulated metabolic pathways plays a role in progression of HCC and liver diseases involved in HCC via ferroptosis. Here, we review physiological role of liver in processing iron ion, our current understanding of iron metabolism, characteristics of ferroptosis, and mechanisms that regulate ferroptosis. In addition, we summarize the role of ferroptosis in the pathogenesis of HCC, including chronic viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis. Finally, we discuss the therapeutic potential of targeting ferroptosis for managing HCC. Summary Emerging evidence supports the notion that dysregulated metabolic pathways and impaired iron homeostasis play a role in progression of HCC and liver diseases that are involved in HCC via ferroptosis. Here, we review physiological role of liver in processing iron ion and summarize the role of ferroptosis in pathogenesis of HCC.