The role of copper and cuproptosis in digestive system cancers: novel therapeutic strategies and mechanistic insights

Recent research has highlighted the critical role of copper metabolism and a novel form of copper-dependent cell death, termed cuproptosis, in the progression and treatment of these cancers. Copper, an essential trace element, plays a crucial role in various cellular processes, including mitochondrial function, antioxidant defense, and angiogenesis. However, the dysregulation of copper homeostasis in cancer cells can exacerbate genomic instability, promote angiogenesis, and reshape the immune microenvironment, thereby driving tumor progression. This review systematically explores the mechanisms of copper homeostasis and cuproptosis in digestive system cancers. We also explore innovative strategies for overcoming drug resistance and reshaping immune responses through copper chelators, copper ionophores, and nanomedicines that induce cuproptosis. By integrating basic research with clinical evidence, this review aims to provide a scientific perspective on understanding the biological significance of cuproptosis and developing new anticancer strategies, while also stimulating in-depth thinking on the intersection of metabolic intervention and cell death.