Mechanistic insights into ferroptosis and its therapeutic potential in hepatocellular carcinoma.

Ferroptosis is an iron-dependent form of programmed cell death driven by lipid peroxidation, distinct from apoptosis and necrosis. It has been confirmed as a key regulator in hepatocellular carcinoma (HCC). This study systematically elucidates three interconnected regulatory networks of ferroptosis-metabolic, epigenetic, and microenvironmental-and proposes a closed-loop regulatory model integrating these dimensions. By integrating metabolic biomarkers, epigenetic indicators, and microenvironmental features, we also summarize emerging strategies to enhance ferroptosis sensitivity. By summarizing the regulatory nodes as well as clinical translation progress, this work provides a comprehensive roadmap for overcoming therapeutic bottlenecks in HCC and realizing ferroptosis-based precision medicine.