Dharavath Anil, Kaur Sivkan, Mohan P V Drupad, Guru Santosh Kumar
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, Kukatpally, Hyderabad, Telangana, 500037, India.
Apoptosis. 2025 Sep 12. doi: 10.1007/s10495-025-02174-1.
Copper-induced cell death, referred to as cuproptosis, introduces a new approach for cancer treatment by utilizing the toxic effects of copper. While copper is vital for enzymatic processes, it becomes harmful at excessive concentrations. Cuproptosis is characterized by mitochondrial impairment resulting from copper interacting with lipoylated components of the tricarboxylic acid (TCA) cycle, leading to proteotoxic stress and targeted cell death. This mechanism is distinct from traditional apoptosis and necrosis. Disruption of copper balance and associated genes, such as FDX1, LIAS, and DLAT, has been linked to various types of cancer. In this review, we outline the timeline of cuproptosis discovery and its comparison with other cell death mechanisms. In addition, we discuss copper homeostasis and copper metabolism in normal human physiology. We also reviewed how the disruption of copper balance can lead to cuproptosis and its involvement in tumorigenesis. Furthermore, we provided an overview of the various genes associated with cuproptosis and their roles in cancer. Given the numerous targets identified, we also provide a thorough overview of the drugs linked to cuproptosis and discuss their clinical relevance and prospects. This review indicates that targeting cuproptosis may serve as a novel therapeutic approach for cancer treatment.
铜诱导的细胞死亡，即铜死亡，通过利用铜的毒性作用为癌症治疗引入了一种新方法。虽然铜对酶促过程至关重要，但在浓度过高时会变得有害。铜死亡的特征是铜与三羧酸（TCA）循环的脂酰化成分相互作用导致线粒体损伤，从而导致蛋白质毒性应激和靶向细胞死亡。这种机制不同于传统的细胞凋亡和坏死。铜平衡及相关基因（如FDX1、LIAS和DLAT）的破坏与各种类型的癌症有关。在这篇综述中，我们概述了铜死亡发现的时间线及其与其他细胞死亡机制的比较。此外，我们讨论了正常人体生理学中的铜稳态和铜代谢。我们还回顾了铜平衡的破坏如何导致铜死亡及其在肿瘤发生中的作用。此外，我们概述了与铜死亡相关的各种基因及其在癌症中的作用。鉴于已确定了众多靶点，我们还全面概述了与铜死亡相关的药物，并讨论了它们的临床相关性和前景。这篇综述表明，靶向铜死亡可能成为一种新型的癌症治疗方法。
