Abstract: Drug resistance is a complicated process with multiple gene and signaling pathways. Multiple evidences demonstratethat reactive oxygen species (ROS) unbalance inducing oxidative stress defense and ROS-related ferroptosis are significantly involved in drug resistance. Recently, it has been found that tumor cells may significantly enhance their ability of oxidative stress defense by negatively regulating ferroptosis, leading to resistant survival. Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxides. The lethal metabolic imbalance caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of it. In a drug-resistant environment, small molecule compound-induced ferroptosis strongly inhibits tumor growth and enhances chemotherapeutic drug sensitivity, suggesting the importance in the treatment of drug resistance. However, the accurate regulation of ferroptosis remains unsure. This review outlined the mechanisms of resistance to oxidative stress in tumor cells, highlighted the role of ferroptosis in drug resistance, and discussed the potential strategies for tumor drug resistance therapy.

Key words: Ferroptosis, Chemotherapy resistance, Iron metabolism, Glutathione