Zhou Yun-Fei, Zhu Yi-Wen, Hao Meng-Yuan, Li Hong-Jie, Han Hang-Shen, Li Yan-Ge, Si Wei-Rong, Jiang Qi-Ying, Wu Dong-Dong
Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, 475004, Henan, China.
School of Medicine, Henan University, Kaifeng, 475004, Henan, China.
Apoptosis. 2025 Aug 7. doi: 10.1007/s10495-025-02150-9.
Liver cancer (LC) stands as one of the most prevalent and highly malignant tumors globally, with persistently elevated mortality rates. For advanced-stage LC, identifying efficacious treatment modalities remains a critical imperative. Cuproptosis, a newly identified form of regulated cell death, exhibits therapeutic potential for impeding LC progression. However, the current clinical evidence remains limited, meriting further in-depth investigation by researchers. Existing literature has summarized copper homeostasis, the molecular mechanisms of cuproptosis, and its roles in certain cancers. However, key challenges in clinical translation haven't been included in the research scope, such as the mechanistic complexity, poor targeting specificity, lack of mature biomarkers, and risk of therapeutic resistance. Notably, the lessons from failed clinical trials have not been fully integrated into ongoing investigations. This review systematically delineates cuproptosis-associated biomarkers in LC, critically analyzes the challenges of targeting cuproptosis for LC therapy and discusses potential solutions. By highlighting current research gaps, we aim to provide actionable research directions for future investigations.
肝癌（LC）是全球最常见且恶性程度极高的肿瘤之一，死亡率持续居高不下。对于晚期肝癌，确定有效的治疗方式仍然是一项至关重要的任务。铜死亡是一种新发现的程序性细胞死亡形式，在阻碍肝癌进展方面具有治疗潜力。然而，目前的临床证据仍然有限，值得研究人员进一步深入研究。现有文献已经总结了铜稳态、铜死亡的分子机制及其在某些癌症中的作用。然而，临床转化中的关键挑战尚未纳入研究范围，例如机制复杂性、靶向特异性差、缺乏成熟的生物标志物以及治疗耐药风险。值得注意的是，失败临床试验的经验教训尚未完全融入正在进行的研究中。本综述系统地阐述了肝癌中与铜死亡相关的生物标志物，批判性地分析了针对肝癌治疗靶向铜死亡的挑战，并讨论了潜在的解决方案。通过突出当前的研究差距，我们旨在为未来的研究提供可行的研究方向。
