Ferroptosis as a Therapeutic Vulnerability to Overcome Chemoresistance in Gastric Cancer

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with treatment outcomes often severely constrained by the emergence of chemoresistance. Ferroptosis, a regulated, iron-dependent form of cell death driven by lethal lipid peroxidation, is a vulnerability that cancer cells actively evade to survive. Its dysregulation has been increasingly linked to therapeutic resistance across multiple malignancies, including GC. Dysregulation of the cystine–glutathione–GPX4 antioxidant system, iron metabolism, and lipid remodeling allows tumor cells to escape ferroptosis, but targeting ferroptosis represents a promising strategy to overcome therapeutic resistance and restore sensitivity to cancer treatments. This review discusses the molecular regulation of ferroptosis, its contribution to chemoresistance, and translational strategies to exploit ferroptosis in cancer therapy.