Wang Jinjiang, Li Jiaxi, Liu Jiao, Chan Kit-Ying, Lee Ho-Sze, Lin Kenneth Nansheng, Wang Chi-Chiu, Lau Tat-San
Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong.
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Cancers (Basel). 2024 Jan 24;16(3):512. doi: 10.3390/cancers16030512.
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）和铜（Cu）作为必需的过渡金属，在对癌症生物学至关重要的各种细胞过程中发挥着关键作用，包括细胞增殖、线粒体呼吸、远处转移和氧化应激。铁死亡和铜死亡作为非凋亡性细胞死亡的不同形式的出现，增强了它们的重要性，特别是与这些金属离子相关。虽然最初是分别研究的，但最近的证据强调了铁死亡和铜死亡的相互依赖性。研究揭示了线粒体铜积累与铁死亡诱导之间的联系。这种相互关联的关系提出了一种有前景的策略，特别是对于解决以耐药性为特征的难治性癌症。在临床环境中利用铁和铜的毒性变得至关重要。同时靶向铁死亡和铜死亡，以索拉非尼和依斯氯醇 - 铜的组合为例，代表了一种引人入胜的方法。靶向线粒体的策略进一步提高了这些方法的精确性，为改善耐药性癌症的治疗结果带来了希望。此外，铁螯合剂和降低铜的药物与既定治疗方式的组合表现出协同作用，有望增强各种恶性肿瘤的抗肿瘤疗效。本综述阐述了铁死亡和铜死亡之间的复杂相互作用，包括其潜在机制，并探讨了它们在癌症研究和临床环境中作为可药物靶向的潜力。
