Yao Leyi, Jiang Baoyi, Xu Dacai
Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang 524033, Guangdong, China.
Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang 524033, Guangdong, China.
Cancer Drug Resist. 2025 Mar 26;8:15. doi: 10.20517/cdr.2025.41. eCollection 2025.
Cancer cells often develop tolerance to chemotherapy, targeted therapy, and immunotherapy drugs either before or during treatment. The significant heterogeneity among various tumors poses a critical challenge in modern cancer research, particularly in overcoming drug resistance. Copper, as an essential trace element in the body, participates in various biological processes of diseases, including cancers. The growth of many types of tumor cells exhibits a heightened dependence on copper. Thus, targeting copper metabolism or inducing cuproptosis may be potential ways to overcome cancer drug resistance. Copper chelators have shown potential in overcoming cancer drug resistance by targeting copper-dependent processes in cancer cells. In contrast, copper ionophores, copper-based nanomaterials, and other small molecules have been used to induce copper-dependent cell death (cuproptosis) in cancer cells, including drug-resistant tumor cells. This review summarizes the regulation of copper metabolism and cuproptosis in cancer cells and the role of copper metabolism and cuproptosis in cancer drug resistance, providing ideas for overcoming cancer resistance in the future.
癌细胞常常在治疗前或治疗期间对化疗、靶向治疗和免疫治疗药物产生耐受性。各种肿瘤之间显著的异质性给现代癌症研究带来了严峻挑战，尤其是在克服耐药性方面。铜作为人体必需的微量元素，参与包括癌症在内的各种疾病的生物学过程。许多类型肿瘤细胞的生长对铜表现出更高的依赖性。因此，靶向铜代谢或诱导铜死亡可能是克服癌症耐药性的潜在途径。铜螯合剂已显示出通过靶向癌细胞中依赖铜的过程来克服癌症耐药性的潜力。相比之下，铜离子载体、铜基纳米材料和其他小分子已被用于诱导癌细胞（包括耐药肿瘤细胞）发生依赖铜的细胞死亡（铜死亡）。本文综述了癌细胞中铜代谢和铜死亡的调控以及铜代谢和铜死亡在癌症耐药性中的作用，为未来克服癌症耐药性提供思路。
