State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, 361102, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, 361102, China.
ChemMedChem. 2024 Nov 4;19(21):e202400216. doi: 10.1002/cmdc.202400216. Epub 2024 Aug 23.
Copper, as an essential trace nutrient for human, plays a crucial role in numerous cellular activities, and is vital for maintaining homeostasis in organisms. Deviations from normal intracellular copper concentration range can disrupt the cellular homeostasis and lead to cell death. Cell death is the process in which cells lose their vitality and cannot sustain normal metabolism, which has various forms. The recently discovered cuproptosis mechanism differs from the previously recognized forms, which is triggered by intracellular copper accumulation. The discovery of cuproptosis has sparked interest among researchers, and this mechanism has been applied in the treatment of various intractable diseases, including different types of cancer. However, the developed cuproptosis-based therapies have revealed certain limitations, such as low immunostimulatory efficiency, poor tumor targeting, and inhibition by the tumor microenvironment. Therefore, researchers are devoted to combining cuproptosis with existing cancer therapies to develop more effective synergistic cancer therapies. This review summarizes the latest research advancements in the cuproptosis-based therapies for various types of cancer, with a focus on the synergistic cancer therapies. Finally, it provides an outlook on the future development of cuproptosis in anti-tumor therapy.
铜作为人体必需的微量元素，在众多细胞活动中发挥着关键作用，对维持生物体的内环境稳定至关重要。细胞内铜浓度的正常范围的偏离会破坏细胞内环境平衡，导致细胞死亡。细胞死亡是指细胞失去活力，无法维持正常代谢的过程，其具有多种形式。最近发现的铜死亡机制与之前公认的形式不同，它是由细胞内铜积累引发的。铜死亡的发现引起了研究人员的兴趣，该机制已应用于治疗各种难治性疾病，包括不同类型的癌症。然而，已开发的基于铜死亡的疗法显示出一定的局限性，例如免疫刺激效率低、肿瘤靶向性差以及肿瘤微环境的抑制。因此，研究人员致力于将铜死亡与现有的癌症疗法相结合，以开发更有效的协同癌症疗法。本综述总结了基于铜死亡的各种类型癌症疗法的最新研究进展，重点介绍了协同癌症疗法。最后，对铜死亡在抗肿瘤治疗中的未来发展进行了展望。
