铜死亡机制及相关抗癌药物

Cuproptosis:mechanisms and anticancer drug development

作为一种必需的微量营养素,铜(copper,Cu)在促进代谢和维持各种基本生物学功能中发挥重要作用。人体内铜的稳态受到严格调控,铜稳态失衡会导致代谢异常并对细胞产生毒性作用。铜死亡是一种新发现的由细胞内过量铜引起的程序性细胞死亡形式,不同于其他已知的细胞死亡途径,在癌症治疗中显示出巨大的潜力。本文系统总结了铜稳态与铜代谢、铜与癌症之间的关系、基于铜复合物的癌症治疗策略、铜死亡机制的发现及基于铜死亡机制的抗癌药物研究进展,旨在为探索基于铜死亡的癌症治疗策略提供思路。

As an essential micronutrient,copper plays an important role in promoting metabolism and maintaining various basic biological function.The homeostasis of copper is tightly regulated and imbalance of copper homeostasis can lead to metabolic abnormalities and toxic effects on cells.Cuproptosis is a newly discovered pathway of programmed cell death induced by excess cellular Cu^(2+).Distinct from all other known pathways underlying cell death,cuproptosis shows great potential in cancer treatment.This review summarizes our current knowledge regarding copper metabolism and copper homeostasis,the link between copper and cancer,Cu complexes in cancer therapy and mechanism of cuproptosis.In addition,the potential therapeutic strategies targeting cuproptosis against cancer are discussed to provide some enlightenment for future research.