Innovative cross-intervention:copper ions and metabolic pathways in cancer therapyOA
Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
Lili Niu;Wei Su;Lixia Ju;Jun Xiang;Zhou Yang;Bing Yao
Department of Integrative Medicine,Shanghai Pulmonary Hospital,Thoracic Cancer Institute,Tongji University School of Medicine,Shanghai 200433,China Department of Cancer Biology,Gastroenterology and Hepatology,Mayo Clinic,Jacksonville,Florida 32224,USADepartment of Medical Oncology,Fudan University Shanghai Cancer Center,Shanghai,China Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,ChinaDepartment of Integrative Medicine,Shanghai Pulmonary Hospital,Thoracic Cancer Institute,Tongji University School of Medicine,Shanghai 200433,ChinaDepartment of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China Department of Head and Neck Surgery,Fudan University Shanghai Cancer Center,Shanghai,ChinaDepartment of Medical Oncology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,ChinaNational Experimental Teaching Center of Basic Medical Science,Department of Medical Genetics,School of Basic Medical Sciences,Nanjing Medical University,Nanjing 211166,China Department of General Surgery,The Affiliated Taizhou People’s Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Nanjing Medical University,Nanjing 211166,China State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,NHC Key Laboratory of Antibody Technique,Jiangsu Province Engineering Research Center of Antibody Drug,Nanjing Medical University,Nanjing 211166,China
医药卫生
Copper homeostasiscuproptosistumor metabolismnanotherapyhypoxia resistance
《Cancer Biology & Medicine》 2026 (1)
P.30-41,12
supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
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