Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.
铁（Fe）与铜（Cu）作为必需的过渡金属，在细胞增殖、线粒体呼吸、远端转移及氧化应激等癌症生物学关键细胞过程中发挥核心作用。铁死亡和铜死亡作为非凋亡性细胞死亡的特殊形式，其发现进一步凸显了这两种金属离子在肿瘤发展中的重要性。尽管最初被独立研究，近期证据表明铁死亡与铜死亡之间存在相互依赖关系。研究显示，线粒体内铜的积累与铁死亡的诱导存在关联。这种相互交织的关系为治疗策略提供了新思路，尤其对于以药物耐受为特征的难治性癌症具有重要潜力。在临床应用中利用铁与铜的毒性作用变得至关重要。同时靶向铁死亡与铜死亡——例如联合使用索拉非尼与艾乐司莫-铜复合物——已成为一种值得关注的策略。针对线粒体的靶向策略进一步提升了此类方法的精准性，为改善耐药性癌症的治疗效果带来了希望。此外，铁螯合剂与降铜剂联合现有治疗模式可产生协同效应，有望增强多种恶性肿瘤的抗肿瘤疗效。本综述系统阐述了铁死亡与铜死亡之间复杂的相互作用机制，并探讨了它们在癌症研究与临床实践中作为药物靶点的潜在价值。
肿瘤(癌症)患者之家