Lipid metabolism in ferroptosis: Unraveling key mechanisms and therapeutic potential in cancer

Abstract

Ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation, has emerged as a critical area of research for cancer therapy. This review delves into the intricate relationship between lipid metabolism and ferroptosis, emphasizing the impact of lipidome remodeling on cancer cell susceptibility. We explore key mechanisms, such as the role of polyunsaturated fatty acids and phosphatidylethanolamines in ferroptosis induction, alongside the protective effects of monounsaturated fatty acids and their regulatory enzymes. We also discuss the influence of dietary fatty acids, lipid droplets, and the epithelial-to-mesenchymal transition on ferroptosis and cancer resistance. By integrating current findings on enzymatic regulation, lipid peroxidation pathways, and metabolic adaptations, this review highlights potential therapeutic strategies targeting lipid metabolism to enhance ferroptosis-based cancer treatments. Our goal is to provide a comprehensive overview that underscores the significance of lipid metabolic pathways in ferroptosis and their implications for developing novel cancer therapies.