Cuproptosis: a novel mechanism and 3PM-oriented therapeutic strategy for cancer
Ding Yang1, Wei-Ting Hu1, Miao Li1
1Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.
Abstract:
Copper overload induces cuproptosis, a unique mitochondria regulated cell death distinct from apoptosis, pyroptosis and ferroptosis. Cuproptosis is involved in cancer progression, drug resistance and immune microenvironment remodeling, making it a promising target for cancer intervention. Key regulators including Copper Transport Protein 1 (CTR1) and Ferredoxin 1 (FDX1) serve as predictive biomarkers: high FDX1 expression indicates enhanced sensitivity to cuproptosis inducers and favorable prognosis in non-small cell lung cancer, supporting precise risk stratification under the Predictive, Preventive and Personalized Medicine(3PM) framework. This review summarizes the molecular mechanisms of cuproptosis and its multifaceted roles in cancer within Predictive, Preventive and Personalized Medicine. Curcumin exhibits potential in modulating cuproptosis homeostasis for high-risk populations with copper overload or precancerous lesions, providing a feasible preventive strategy. We also discuss cuproptosis-targeted therapies, combination regimens and the value of traditional Chinese medicine, while clarifying crosstalk with other cell death pathways. This review addresses the clinical gap of lacking effective predictive and preventive targets for precision oncology, offering novel 3PM-oriented insights for cancer diagnosis, prevention and treatment.
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