Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.

Copper (Cu), as an essential trace element, is involved in a variety of key biological processes, such as mitochondrial respiratory chain, antioxidant defense, and cellular signal transduction. It is also potentially toxic while maintaining life activities: once intracellular free copper increases or becomes imbalanced, it may trigger a cascade of stress responses, including protein misfolding, disruption of redox homeostasis, and mitochondrial dysfunction. Therefore, the body maintains copper homeostasis through fine-tuned uptake, transport, storage, and efflux systems, ensuring copper remains in dynamic balance. Tumor cells often undergo adaptive changes in metal ion homeostasis in response to metabolic reprogramming and microenvironmental selective pressures. Abnormal copper metabolism has been considered closely related to tumor development, invasion, metastasis, and treatment tolerance. In recent years, cuproptosis has provided a new theoretical framework for studying the relationship between copper and tumors. Our manuscript expounds on the therapeutic value of copper and cuproptosis in tumor progression and treatment, providing a new entry point for updating accurate cancer treatment strategies.