Wang Hongyu, Yang Yawen, Du Juan
Department of Abdominal Oncology, Jilin Cancer Hospital, Changchun, 130000, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 21. doi: 10.1007/s00210-025-04263-z.
Colorectal cancer (CRC) represents a prevalent neoplastic disorder of the digestive tract, characterized by elevated incidence and mortality rates. The cellular metabolism of copper within CRC cells is frequently dysregulated, indicating that modifications to copper concentrations may induce cell death and potentially enhance the overall suppression of tumor progression. Cuproptosis, a recently identified form of cellular death, occurs when copper ions bind directly to the lipoylated components of the citric acid cycle (CAC) within mitochondrial respiration, thereby disrupting the balance of iron-sulfur cluster (Fe-S cluster) proteins and ultimately leading to protein toxic stress. The defining traits of cuproptosis include dependence on Cu2 concentrations and pronounced expression in cells engaged in mitochondrial respiration. This novel mechanism has attracted significant interest within the cancer research community due to its substantial therapeutic potential in oncology. Treatments based on copper demonstrate an inhibitory effect on tumor proliferation and may facilitate approaches for treating tumors that are resistant to conventional chemotherapy. This article aims to review the significance of cuproptosis in CRC, positing that it may serve as a promising strategy for antitumor therapy and an innovative treatment paradigm to address drug resistance in cancer.
结直肠癌（CRC）是一种常见的消化道肿瘤性疾病，其发病率和死亡率都很高。CRC细胞内铜的细胞代谢常常失调，这表明改变铜浓度可能会诱导细胞死亡，并有可能增强对肿瘤进展的整体抑制作用。铜死亡是一种最近发现的细胞死亡形式，当铜离子直接与线粒体呼吸中柠檬酸循环（CAC）的脂酰化成分结合时就会发生，从而破坏铁硫簇（Fe-S簇）蛋白的平衡，最终导致蛋白质毒性应激。铜死亡的决定性特征包括对Cu2+浓度的依赖性以及在参与线粒体呼吸的细胞中显著表达。这种新机制因其在肿瘤学中的巨大治疗潜力而在癌症研究领域引起了极大关注。基于铜的治疗方法对肿瘤增殖具有抑制作用，并且可能有助于治疗对传统化疗耐药的肿瘤。本文旨在综述铜死亡在CRC中的意义，认为它可能是一种有前景的抗肿瘤治疗策略和解决癌症耐药性的创新治疗模式。
