Ferroptosis and its emerging role in tumor

Abstract

Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation accumulation. It is morphologically, biochemically, and genetically distinct from other known cell death, such as apoptosis, necrosis, and pyroptosis. Its regulatory mechanisms include iron metabolism, fatty acid metabolism, mitochondrial respiration, and antioxidative systems eliminating lipid peroxidation, such as glutathione synthesis, selenium-dependent glutathione peroxidase 4, and ubiquinone. The disruption of cellular redox systems causes damage to the cellular membrane leading to ferroptotic cell death. Recent studies have shown that numerous pathological diseases, like tumors, neurodegenerative disorders, and ischemia-reperfusion injury are associated with ferroptosis. As such, pharmacological regulation of ferroptosis either by activation or by suppression will provide a vast potential for treatments of relevant diseases. This review will discuss the advanced progress in ferroptosis and its regulatory mechanisms from both the antioxidative and oxidative sides. In addition, the roles of ferroptosis in various tumorigenesis, development, and therapeutic strategies will be addressed, particularly to chemotherapy and immunotherapy, as well as the discoveries from Traditional Chinese Medicine. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy.

Graphical abstract

Keywords

Ferroptosis / Cancer / Cell death / GPX4