The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy

International audienceIn the human body, copper (Cu) is a major and essential player in a large number of cellularmechanisms and signaling pathways. The involvement of Cu in oxidation–reduction reactionsrequires close regulation of copper metabolism in order to avoid toxic effects. In many types ofcancer, variations in copper protein levels have been demonstrated. These variations result inincreased concentrations of intratumoral Cu and alterations in the systemic distribution of copper.Such alterations in Cu homeostasis may promote tumor growth or invasiveness or may even conferresistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing severalpromising biomarkers for clinical use with prognostic or predictive capabilities. The altered Cumetabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting thedevelopment of treatments to disrupt, deplete, or increase Cu levels in tumors. The metallic natureof Cu as a chemical element is key for the development of anticancer agents via the synthesis ofnanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some ofthese new therapeutic strategies such as chelators or ionophores have shown promising results in apreclinical setting, and others are already in the clinic