Ferroptosis in hepatocellular carcinoma: Mechanisms and therapeutic implications

Ferroptosis is a novel form of oxidative cell death, in which highly expressed unsaturated fatty acids on the cell membrane are catalyzed by divalent iron or ester oxygenase to promote liposome peroxidation. This process reduces cellular antioxidant capacity, increases lipid reactive oxygen species, and leads to the accumulation of intracellular ferrous ions, which disrupts intracellular redox homeostasis and ultimately causes oxidative cell death. Studies have shown that ferroptosis induces an immune response that has a dual role in liver disease, ferroptosis also offers a promising strategy for precise cancer therapy. Ferroptosis regulators are beneficial in maintaining cellular homeostasis and tissue health, have shown efficacy in treating diseases of the hepatic system. However, the mechanisms of action and molecular regulatory pathways of ferroptosis in hepatocellular carcinoma (HCC) have not been fully elucidated. Therefore, deciphering the role of ferroptosis and its mechanisms in HCC progression is crucial for treating the disease. In this review, we introduce the morphological features and biochemical functions of ferroptosis, outline the molecular regulatory pathways of ferroptosis, and highlights the therapeutic potential of ferroptosis inhibitors and modulators to target it in HCC.