Liu Jingwen, Huang Hairuo, Zhang Xiaojie, Shen Yang, Jiang DeMing, Hu Shurong, Li Shuyan, Yan Zelin, Hu Wen, Luo Jinhua, Yao Haibo, Chen Yan, Tang Bufu
Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
China Medical University, Shenyang 110122, China.
Research (Wash D C). 2025 May 14;8:0698. doi: 10.34133/research.0698. eCollection 2025.
Cuproptosis represents a novel mechanism of cellular demise characterized by the intracellular buildup of copper ions. Unlike other cell death mechanisms, its distinct process has drawn considerable interest for its promising applications in managing inflammatory bowel disease (IBD) and colorectal cancer (CRC). Emerging evidence indicates that copper metabolism and cuproptosis may exert dual regulatory effects within pathological cellular environments, specifically modulating oxidative stress responses, metabolic reprogramming, and immunotherapeutic efficacy. An appropriate level of copper may promote disease progression and exert synergistic effects, but exceeding a certain threshold, copper can inhibit disease development by inducing cuproptosis in pathological cells. This makes abnormal copper levels a potential new therapeutic target for IBD and CRC. This review emphasizes the dual function of copper metabolism and cuproptosis in the progression of IBD and CRC, while also exploring the potential application of copper-based therapies in disease treatment. The analysis further delineates the modulatory influence of tumor immune microenvironment on cuproptosis dynamics, while establishing the therapeutic potential of cuproptosis-targeted strategies in circumventing resistance to both conventional chemotherapeutic agents and emerging immunotherapies. This provides new research directions for the development of future cuproptosis inducers. Finally, this article discusses the latest advances in potential molecular targets of cuproptosis and their related genes in the treatment of IBD and CRC, highlighting future research priorities and unresolved issues.
铜死亡代表了一种新的细胞死亡机制，其特征是细胞内铜离子积累。与其他细胞死亡机制不同，其独特的过程因其在治疗炎症性肠病（IBD）和结直肠癌（CRC）方面的潜在应用而引起了广泛关注。新出现的证据表明，铜代谢和铜死亡可能在病理细胞环境中发挥双重调节作用，特别是调节氧化应激反应、代谢重编程和免疫治疗效果。适当水平的铜可能促进疾病进展并发挥协同作用，但超过一定阈值时，铜可通过诱导病理细胞中的铜死亡来抑制疾病发展。这使得异常的铜水平成为IBD和CRC潜在的新治疗靶点。本综述强调了铜代谢和铜死亡在IBD和CRC进展中的双重作用，同时还探讨了基于铜的疗法在疾病治疗中的潜在应用。分析进一步阐述了肿瘤免疫微环境对铜死亡动态的调节影响，同时确立了靶向铜死亡策略在规避对传统化疗药物和新兴免疫疗法耐药性方面的治疗潜力。这为未来铜死亡诱导剂的开发提供了新的研究方向。最后，本文讨论了铜死亡潜在分子靶点及其相关基因在IBD和CRC治疗中的最新进展，突出了未来的研究重点和未解决的问题。
