Xianmei Lv,1,2,* Gaochen Lan,3,* Lujian Zhu,4,* Qiusheng Guo1 

1Department of Radiotherapy, Jinhua People’s Hospital, Jinhua, Zhejiang, 321000, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 3Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China; 4Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qiusheng Guo, Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Email zhanluzhihun@126.com

Abstract: Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance.

Keywords: ferroptosis, hepatocellular carcinoma, chemotherapy, tyrosine kinase inhibitor, immunosuppressive therapy, radiotherapy