The in vivo metabolic mechanism of copper and its therapeutic potential in related diseases

This review systematically elucidates the metabolic mechanisms of essential trace element copper in humans, including absorption, distribution, storage, excretion, and homeostatic regulation. It emphasizes copper's role in participating in various biochemical reactions and maintaining protein structure and function through the redox conversion between cupric ions and cuprous state (or Cu⁺), as well as the pathological basis by which excessive free copper induces the production of reactive oxygen species and thereby triggers cellular damage. The review emphasizes the association of copper homeostasis dysregulation with multiple diseases, such as liver disorders, neurodegenerative conditions, cardiovascular diseases, and copper-related genetic diseases. It further explores copper's role in cancer biology, particularly its promotion of tumor initiation, proliferation, angiogenesis, and metastasis via signaling pathways, with a focus on the “copper proliferation”-mediated malignant transformation mechanisms. Additionally, recent advances and clinical potential of copper-targeted anticancer strategies, including copper chelators, ionophores, and complexes are discussed. Finally, the article addresses current challenges in copper-targeted therapies, such as therapeutic heterogeneity across different cancer types and patient populations, and the incomplete understanding of copper signaling networks. Future perspectives are provided, highlighting precision medicine approaches, combination therapies, and novel drug development, aiming to deepen the understanding of copper-related pathology and foster the development of innovative cancer treatments.