Chen Xiaoyan, Huang Luanluan, Liu Ruiqi, Nan Ding, Li Yucheng, Chen Weijun, Shi Lei, Wang Ying, Liang Xiaodong, Tang Jianming, Zhang Haibo, Lu Yanwei
Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Department of Pathology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Int Immunopharmacol. 2026 Jan 1;168(Pt 1):115788. doi: 10.1016/j.intimp.2025.115788. Epub 2025 Nov 8.
Cuproptosis is a novel, copper-dependent regulated cell death (RCD) pathway identified in 2022. It is distinct from other forms of cell death, such as ferroptosis, due to its unique mechanism involving mitochondrial copper overload, aggregation of lipoylated TCA-cycle proteins, and subsequent proteotoxic stress. Although secondary reactive oxygen species (ROS) production may occur, cuproptosis is not driven by lipid peroxidation, highlighting its specificity. The significance of cuproptosis extends beyond cancer, notably to neurodegenerative disorders such as Alzheimer's disease (AD), where copper dyshomeostasis exacerbates pathology. In oncology, cuproptosis induction has emerged as a promising therapeutic strategy, with agents including copper ionophores, nanomaterials, and repurposed drugs showing efficacy. This review highlights the molecular uniqueness of cuproptosis, its clinical relevance, and translational challenges in therapeutic applications.
