Cuproplasia and cuproptosis, two sides of the coin

Abstract Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evas...

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Main Authors: Kaizhong Lu, Chandra Sugiarto Wijaya, Qinghua Yao, Hongchuan Jin, Lifeng Feng
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Cancer Communications
Subjects:
Online Access:https://doi.org/10.1002/cac2.70001
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author Kaizhong Lu
Chandra Sugiarto Wijaya
Qinghua Yao
Hongchuan Jin
Lifeng Feng
author_facet Kaizhong Lu
Chandra Sugiarto Wijaya
Qinghua Yao
Hongchuan Jin
Lifeng Feng
author_sort Kaizhong Lu
collection DOAJ
description Abstract Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming the copper regulatory network, defined as cuproplasia. Thus, targeting copper chelation to reduce copper levels has been considered a rational tumor therapy strategy. However, overloaded copper ions could be toxic, which leads to the aggregation of lipoylated mitochondrial proteins and the depletion of iron‐sulfur clusters, ultimately resulting in cell death, termed cuproptosis. Upon its discovery, cuproptosis has attracted great interest from oncologists, and targeting cuproptosis by copper ionophores exhibits as a potential anti‐tumor therapy. In this review, we present the underlying mechanisms involved in cuproplasia and cuproptosis. Additionally, we sum up the chemicals targeting either cuproplasia or cuproptosis for cancer therapy. Further attention should be paid to distinguishing cancer patients who are suitable for targeting cuproplasia or cuproptosis.
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publisher Wiley
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series Cancer Communications
spelling doaj-art-c30b67d364254c82a46d6b41b269ccbc2025-08-20T02:15:19ZengWileyCancer Communications2523-35482025-05-0145550552410.1002/cac2.70001Cuproplasia and cuproptosis, two sides of the coinKaizhong Lu0Chandra Sugiarto Wijaya1Qinghua Yao2Hongchuan Jin3Lifeng Feng4Department of Medical OncologyZhejiang Key Laboratory of Multi‐omics Precision Diagnosis and Treatment of Liver DiseasesCancer Center of Zhejiang UniversitySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP. R. ChinaDepartment of Medical OncologyZhejiang Key Laboratory of Multi‐omics Precision Diagnosis and Treatment of Liver DiseasesCancer Center of Zhejiang UniversitySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP. R. ChinaDepartment of OncologyThe Second Affiliated Hospital of Zhejiang Chinese Medical UniversityXinhua Hospital of Zhejiang ProvinceHangzhouZhejiangP. R. ChinaDepartment of Medical OncologyZhejiang Key Laboratory of Multi‐omics Precision Diagnosis and Treatment of Liver DiseasesCancer Center of Zhejiang UniversitySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP. R. ChinaDepartment of Medical OncologyZhejiang Key Laboratory of Multi‐omics Precision Diagnosis and Treatment of Liver DiseasesCancer Center of Zhejiang UniversitySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangP. R. ChinaAbstract Copper is an essential micronutrient in the human body, mainly acting as a crucial cofactor required for a wide range of physiological processes across nearly all cell types. Recent advances revealed that tumor cells seize copper to fulfill their rapid proliferation, metastasis, immune evasion, and so on by reprogramming the copper regulatory network, defined as cuproplasia. Thus, targeting copper chelation to reduce copper levels has been considered a rational tumor therapy strategy. However, overloaded copper ions could be toxic, which leads to the aggregation of lipoylated mitochondrial proteins and the depletion of iron‐sulfur clusters, ultimately resulting in cell death, termed cuproptosis. Upon its discovery, cuproptosis has attracted great interest from oncologists, and targeting cuproptosis by copper ionophores exhibits as a potential anti‐tumor therapy. In this review, we present the underlying mechanisms involved in cuproplasia and cuproptosis. Additionally, we sum up the chemicals targeting either cuproplasia or cuproptosis for cancer therapy. Further attention should be paid to distinguishing cancer patients who are suitable for targeting cuproplasia or cuproptosis.https://doi.org/10.1002/cac2.70001copper homeostasiscuproplasiacuproptosistumortherapeutics targeting copper
spellingShingle Kaizhong Lu
Chandra Sugiarto Wijaya
Qinghua Yao
Hongchuan Jin
Lifeng Feng
Cuproplasia and cuproptosis, two sides of the coin
Cancer Communications
copper homeostasis
cuproplasia
cuproptosis
tumor
therapeutics targeting copper
title Cuproplasia and cuproptosis, two sides of the coin
title_full Cuproplasia and cuproptosis, two sides of the coin
title_fullStr Cuproplasia and cuproptosis, two sides of the coin
title_full_unstemmed Cuproplasia and cuproptosis, two sides of the coin
title_short Cuproplasia and cuproptosis, two sides of the coin
title_sort cuproplasia and cuproptosis two sides of the coin
topic copper homeostasis
cuproplasia
cuproptosis
tumor
therapeutics targeting copper
url https://doi.org/10.1002/cac2.70001
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AT chandrasugiartowijaya cuproplasiaandcuproptosistwosidesofthecoin
AT qinghuayao cuproplasiaandcuproptosistwosidesofthecoin
AT hongchuanjin cuproplasiaandcuproptosistwosidesofthecoin
AT lifengfeng cuproplasiaandcuproptosistwosidesofthecoin