New dawn for cancer cell death: Emerging role of lipid metabolism

Resistance to cell death, a protective mechanism for removing damaged cells, is a “Hallmark of Cancer” that is essential for cancer progression. Increasing attention to cancer lipid metabolism has revealed a number of pathways that induce cancer cell death. We summarize emerging concepts regarding lipid metabolic reprogramming in cancer that is mainly involved in lipid uptake and trafficking, de novo synthesis and esterification, fatty acid synthesis and oxidation, lipogenesis, and lipolysis. During carcinogenesis and progression, continuous metabolic adaptations are co-opted by cancer cells, to maximize their fitness to the ever-changing environmental. Lipid metabolism and the epigenetic modifying enzymes interact in a bidirectional manner which involves regulating cancer cell death. Moreover, lipids in the tumor microenvironment play unique roles beyond metabolic requirements that promote cancer progression. Finally, we posit potential therapeutic strategies targeting lipid metabolism to improve treatment efficacy and survival of cancer patient. The profound comprehension of past findings, current trends, and future research directions on resistance to cancer cell death will facilitate the development of novel therapeutic strategies targeting the lipid metabolism. •Lipid metabolic reprogramming is crucial for various aspects of cancer cell death.•Cancer cell growth depends on lipid metabolic plasticity and sustained metabolic adaptations.•Lipid metabolism and the epigenome interact in a bidirectional manner, which regulate cancer cell death.•The therapeutic strategies targeting lipid metabolism can improve treatment efficacy and survival of cancer patients.