Copper in melanoma: At the crossroad of protumorigenic and anticancer roles
Copper is an essential micronutrient that is a cofactor for various enzymes involved in multiple cellular processes. Melanoma patients have high serum copper levels, and elevated copper concentrations are found in melanoma tumors. Copper influences the activity of several melanoma-related proteins i...
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Elsevier
2025-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000655 |
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| author | Natalia Chrzan Mariusz L. Hartman |
| author_facet | Natalia Chrzan Mariusz L. Hartman |
| author_sort | Natalia Chrzan |
| collection | DOAJ |
| description | Copper is an essential micronutrient that is a cofactor for various enzymes involved in multiple cellular processes. Melanoma patients have high serum copper levels, and elevated copper concentrations are found in melanoma tumors. Copper influences the activity of several melanoma-related proteins involved in cell survival, proliferation, pigmentation, angiogenesis, and metastasis. Targeting these processes with copper chelators has shown efficacy in reducing tumor growth and overcoming drug resistance. In contrast, excessive copper can also have detrimental effects when imported into melanoma cells. Multiple distinct cellular effects of copper overload, including the induction of different types of cell death, have been reported. Cuproptosis, a novel type of copper-dependent cell death, has been recently described and is associated with the metabolic phenotype. Melanoma cells can switch between glycolysis and oxidative phosphorylation, which are crucial for tumor growth and drug resistance. In this respect, metabolic plasticity might be exploited for the use of copper-delivery strategies, including repurposing of disulfiram, which is approved for the treatment of noncancer patients. In addition, the development of nanomedicines can improve the targeted delivery of copper to melanoma cells and enable the use of these drugs alone or in combination as copper has been shown to complement targeted therapy and immunotherapy in melanoma cells. However, further research is needed to explore the specific mechanisms of both copper restriction and excess copper-induced processes and determine effective biomarkers for predicting treatment sensitivity in melanoma patients. In this review, we discuss the dual role of copper in melanoma biology. |
| format | Article |
| id | doaj-art-fa8e8e97cf6f491786d8a16c69bbafce |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Redox Biology |
| spelling | doaj-art-fa8e8e97cf6f491786d8a16c69bbafce2025-08-20T02:07:17ZengElsevierRedox Biology2213-23172025-04-018110355210.1016/j.redox.2025.103552Copper in melanoma: At the crossroad of protumorigenic and anticancer rolesNatalia Chrzan0Mariusz L. Hartman1Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215, Lodz, PolandCorresponding author.; Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215, Lodz, PolandCopper is an essential micronutrient that is a cofactor for various enzymes involved in multiple cellular processes. Melanoma patients have high serum copper levels, and elevated copper concentrations are found in melanoma tumors. Copper influences the activity of several melanoma-related proteins involved in cell survival, proliferation, pigmentation, angiogenesis, and metastasis. Targeting these processes with copper chelators has shown efficacy in reducing tumor growth and overcoming drug resistance. In contrast, excessive copper can also have detrimental effects when imported into melanoma cells. Multiple distinct cellular effects of copper overload, including the induction of different types of cell death, have been reported. Cuproptosis, a novel type of copper-dependent cell death, has been recently described and is associated with the metabolic phenotype. Melanoma cells can switch between glycolysis and oxidative phosphorylation, which are crucial for tumor growth and drug resistance. In this respect, metabolic plasticity might be exploited for the use of copper-delivery strategies, including repurposing of disulfiram, which is approved for the treatment of noncancer patients. In addition, the development of nanomedicines can improve the targeted delivery of copper to melanoma cells and enable the use of these drugs alone or in combination as copper has been shown to complement targeted therapy and immunotherapy in melanoma cells. However, further research is needed to explore the specific mechanisms of both copper restriction and excess copper-induced processes and determine effective biomarkers for predicting treatment sensitivity in melanoma patients. In this review, we discuss the dual role of copper in melanoma biology.http://www.sciencedirect.com/science/article/pii/S2213231725000655Cell metabolismCopper ionophoresCuproplasiaCuproptosisMelanomaNanodrugs |
| spellingShingle | Natalia Chrzan Mariusz L. Hartman Copper in melanoma: At the crossroad of protumorigenic and anticancer roles Redox Biology Cell metabolism Copper ionophores Cuproplasia Cuproptosis Melanoma Nanodrugs |
| title | Copper in melanoma: At the crossroad of protumorigenic and anticancer roles |
| title_full | Copper in melanoma: At the crossroad of protumorigenic and anticancer roles |
| title_fullStr | Copper in melanoma: At the crossroad of protumorigenic and anticancer roles |
| title_full_unstemmed | Copper in melanoma: At the crossroad of protumorigenic and anticancer roles |
| title_short | Copper in melanoma: At the crossroad of protumorigenic and anticancer roles |
| title_sort | copper in melanoma at the crossroad of protumorigenic and anticancer roles |
| topic | Cell metabolism Copper ionophores Cuproplasia Cuproptosis Melanoma Nanodrugs |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000655 |
| work_keys_str_mv | AT nataliachrzan copperinmelanomaatthecrossroadofprotumorigenicandanticancerroles AT mariuszlhartman copperinmelanomaatthecrossroadofprotumorigenicandanticancerroles |