TITLE:
Research Progress on the Role of Ferroptosis in the Development of Oxaliplatin Resistance in Gastric Cancer
AUTHORS:
Wancheng Wu, Xudong Xin, Jianchu Wang
KEYWORDS:
Gastric Cancer, Ferroptosis, Oxaliplatin, Drug Resistance, Tumor Microenvironment
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.5,
May
6,
2026
ABSTRACT: Gastric cancer is one of the most common malignant tumors of the digestive tract, with a low rate of early detection and an unsatisfactory overall prognosis in advanced stages. Oxaliplatin-based regimens are widely used in the treatment of advanced gastric cancer; however, acquired resistance limits sustained therapeutic benefit and adversely affects recurrence and survival outcomes. Ferroptosis, a form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation, is jointly regulated by the System Xc−-GSH-GPX4 axis, the FSP1-CoQ10 pathway, and signaling pathways such as p53, and is also influenced by exosomal signaling and metabolic reprogramming within the tumor microenvironment (TME). Current studies indicate that the development of oxaliplatin resistance in gastric cancer is often accompanied by activation of antioxidant systems, elevation of the lipid peroxidation threshold, and suppression of ferroptosis. Induction of ferroptosis through natural compounds or combination strategies has been shown, under certain conditions, to enhance the cytotoxicity of oxaliplatin and partially reverse resistant phenotypes. This review focuses on the molecular mechanisms underlying ferroptosis, summarizes the characteristics of aberrant ferroptosis regulation in gastric cancer, outlines the major pathways through which ferroptosis participates in oxaliplatin resistance, discusses strategies for reversing resistance by inducing ferroptosis, and explores the potential of ferroptosis-related molecules as predictive biomarkers and targets for clinical translation.