Ferroptosis and cuproptosis in gastric cancer: Mechanisms, roles, and potential Interplay

Gastric cancer (GC), a prevalent and lethal malignancy globally, remains a severe health concern because of its high incidence and fatality. Notably, ferroptosis and cuproptosis, both novel kinds of controlled cell death, were discovered to greatly alter GC advancement. Ferroptosis, characterized by iron-induced lipid peroxidation, and cuproptosis, triggered by copper-mediated mitochondrial dysfunction, are intricately interconnected in GC. Their crosstalk involves oxidative stress, mitochondrial tricarboxylic acid (TCA) cycle disruption, autophagy, and glutathione (GSH) metabolism imbalance. Understanding this crosstalk holds great promise for identifying new therapeutic targets. This review comprehensively explores the underlying mechanisms of the ferroptosis-cuproptosis crosstalk in GC, identifies potential therapeutic targets, and discusses future research directions, aiming for offering prevention and treatment strategies for GC.