Li Zhang, Yongpeng Cheng, Lulu Tang, Jiaxing Zhu, Biguang Tuo
In cells, copper levels are tightly regulated because copper deficiency leads to Menkes disease, anemia and neurodegeneration, whereas copper overload is associated with Wilson disease, liver injury, neurodegeneration and several cancers. Cuproptosis, a form of regulated cell death, depends on the intracellular accumulation of excessive copper. This process induces mitochondrial dysfunction and cell death by disrupting the stability of mitochondrial lipoylated proteins and iron‑sulfur cluster proteins. The present review aimed to summarize the mechanisms underlying cuproptosis in gastrointestinal cancer, with a focus on the relationship between copper metabolism imbalance and tumor initiation and progression, as well as the potential therapeutic applications of cuproptosis‑associated agents in oncology. The application prospects of cuproptosis in gastrointestinal tumor therapy are broad, offering novel therapeutic options that may improve prognosis in patients and survival outcomes.