Epigenetic modulation of ferroptosis in cancer: Identifying epigenetic targets for novel anticancer therapy.

Ferroptosis is a newly recognized form of oxidative-regulated cell death resulting from iron-mediated lipid peroxidation accumulation. Radical-trapping antioxidant systems can eliminate these oxidized lipids and prevent disrupting the integrity of cell membranes. Epigenetic modifications can regulate ferroptosis by altering gene expression or cell phenotype without permanent sequence changes. These mechanisms include DNA methylation, histone modifications, RNA modifications, and noncoding RNAs. Epigenetic alterations in cancer can control the expression of ferroptosis regulators or related pathways, leading to changes in cell sensitivity to ferroptosis inducers or cancer progression. Epigenetic alterations in cancer are influenced by a wide range of cancer hallmarks, contributing to therapeutic resistance. Targeting epigenetic alterations is a promising approach to overcoming cancer resilience. However, the exact mechanisms involved in different types of cancer remain unresolved. Discovering more ferroptosis-associated epigenetic targets and interventions can help overcome current barriers in anticancer therapy. Many papers on epigenetic modifications of ferroptosis have been continuously published, making it essential to summarize the current state-of-the-art in the epigenetic regulation of ferroptosis in human cancer.