Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy

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.

Graphical Abstract

Keywords:

• ferroptosis
• hepatocellular carcinoma
• chemotherapy
• tyrosine kinase inhibitor
• immunosuppressive therapy
• radiotherapy

Acknowledgments

This study was funded by the Jinhua traditional Chinese Medicine Science and Technology Research Program Project (2024LC11) and the Health Science and Technology Plan Project of Fujian Province (No. 2022QNA065). We express our gratitude for the provision of the picture materials by Figdraw (www.figdraw.com).

Disclosure

The authors report no conflicts of interest in this work.