Division of Abdominal Cancer, Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Division of Abdominal Cancer, Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
J Hematol Oncol. 2024 Aug 16;17(1):68. doi: 10.1186/s13045-024-01589-8.
Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation of dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and the loss of iron-sulfur cluster proteins, ultimately resulting in proteotoxic stress and triggering cell death. Recently, cuproptosis has garnered significant interest in tumor research due to its potential as a crucial therapeutic strategy against cancer. In this review, we summarized the cellular and molecular mechanisms of cuproptosis and its relationship with other types of cell death. Additionally, we reviewed the current drugs or strategies available to induce cuproptosis in tumor cells, including Cu ionophores, small compounds, and nanomedicine. Furthermore, we targeted cell metabolism and specific regulatory genes in cancer therapy to enhance tumor sensitivity to cuproptosis. Finally, we discussed the feasibility of targeting cuproptosis to overcome tumor chemotherapy and immunotherapy resistance and suggested future research directions. This study suggested that targeting cuproptosis could open new avenues for developing tumor therapy.
铜死亡是一种新发现的细胞死亡形式，由细胞内铜（Cu）积累过多引起。从机制上讲，铜死亡是由 Cu 诱导的二氢硫辛酰胺 S-乙酰转移酶聚集引起的，与线粒体三羧酸循环和铁硫簇蛋白的丧失有关，最终导致蛋白毒性应激并触发细胞死亡。最近，铜死亡因其作为对抗癌症的关键治疗策略的潜力而在肿瘤研究中引起了极大的关注。在这篇综述中，我们总结了铜死亡的细胞和分子机制及其与其他类型细胞死亡的关系。此外，我们还回顾了目前可用于诱导肿瘤细胞铜死亡的药物或策略，包括 Cu 载体、小分子和纳米医学。此外，我们针对癌症治疗中的细胞代谢和特定调节基因来增强肿瘤对铜死亡的敏感性。最后，我们讨论了靶向铜死亡以克服肿瘤化疗和免疫治疗耐药性的可行性，并提出了未来的研究方向。这项研究表明，靶向铜死亡可能为开发肿瘤治疗开辟新途径。
