Metabolic Regulation of Ferroptosis in Cancer

Abstract

Simple Summary Ferroptosis is a recently defined nonapoptotic form of cell death that is associated with various human diseases, including cancer. As ferroptosis is caused by an overdose of lipid peroxidation resulting from dysregulation of the cellular antioxidant system, it is inherently closely associated with cellular metabolism. Here, we provide an updated review of the recent studies that have shown mechanisms of metabolic regulation of ferroptosis in the context of cancer. Ferroptosis is a unique cell death mechanism that is executed by the excessive accumulation of lipid peroxidation in cells. The relevance of ferroptosis in multiple human diseases such as neurodegeneration, organ damage, and cancer is becoming increasingly evident. As ferroptosis is deeply intertwined with metabolic pathways such as iron, cyst(e)ine, glutathione, and lipid metabolism, a better understanding of how ferroptosis is regulated by these pathways will enable the precise utilization or prevention of ferroptosis for therapeutic uses. In this review, we present an update of the mechanisms underlying diverse metabolic pathways that can regulate ferroptosis in cancer.