Copper, an essential trace element that exists in oxidized and reduced forms, has pivotal roles in a variety of biological processes, including redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy and immune modulation; maintaining copper homeostasis is crucial as both its deficiency and its excess are deleterious. Dysregulated copper metabolism has a dual role in tumorigenesis and cancer therapy. Specifically, cuproplasia describes copper-dependent cell growth and proliferation, including hyperplasia, metaplasia and neoplasia, whereas cuproptosis refers to a mitochondrial pathway of cell death triggered by excessive copper exposure and subsequent proteotoxic stress (although complex interactions between cuproptosis and other cell death mechanisms, such as ferroptosis, are likely and remain enigmatic). In this Review, we summarize advances in our understanding of copper metabolism, the molecular machineries underlying cuproplasia and cuproptosis, and their potential targeting for cancer therapy. These new findings advance the rapidly expanding field of translational cancer research focused on metal compounds.

铜是一种以氧化和还原形式存在的必需微量元素，在多种生物过程中发挥着关键作用，包括氧化还原化学、酶反应、线粒体呼吸、铁代谢、自噬和免疫调节；维持铜的稳态至关重要，因为铜的缺乏和过量都是有害的。铜代谢失调在肿瘤发生和癌症治疗中具有双重作用。具体来说，铜形成描述了铜依赖性细胞生长和增殖，包括增生、化生和瘤形成，而铜死亡是指由过量的铜暴露和随后的蛋白毒性应激触发的细胞死亡的线粒体途径（尽管铜死亡和其他细胞死亡机制之间存在复杂的相互作用，例如铁死亡，很可能并且仍然是个谜）。在这篇综述中，我们总结了我们对铜代谢、铜形成和铜死亡的分子机制及其癌症治疗潜在靶点的理解进展。这些新发现推动了以金属化合物为重点的转化癌症研究领域的快速扩展。