REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1685331
This article is part of the Research TopicTargeting Cell Death Pathways for Enhanced Cancer Immunotherapy: Specific Involve in Necroptosis, Pyroptosis, Ferroptosis, Cuproptosis, Autophagy, Apoptosis, and ICD ResearchView all 15 articles
Iron, Copper and Disulfide Dysregulation: Molecular Crossroads of Metabolic Cell Death in Melanoma Progression
Provisionally accepted
- Tianjin University, Tianjin, China
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Melanoma is a highly aggressive malignant tumor arising from melanocytes, with its incidence and mortality rates continuously rising in recent years, posing a major global public health challenge. Although traditional targeted therapies and immune checkpoint inhibitors have significantly improved survival in some patients, primary and acquired resistance remain common, creating an urgent need for new treatment strategies. In recent years, metabolic cell death, ferroptosis, cuproptosis, and disulfidptosis, has shown unique advantages in melanoma research. Ferroptosis directly kills tumor cells through iron-mediated lipid peroxidation; cuproptosis relies on copper-induced mitochondrial protein aggregation to inhibit tumor proliferation; disulfidptosis arises from disulfide stress caused by glucose deprivation. This review provides a detailed analysis of on the mechanisms and metabolic competition paradoxes of these three types of metabolic cell death and integrates key metabolic nodes, such as related genes SLC7A11, GPX4, FDX1, LIPT1, and PPIC. Furthermore, we discuss innovative treatment strategies that significantly enhance therapeutic efficacy and overcome resistance, including the combination of metabolic cell death with immune cell regulation, nanoparticle delivery, and sonodynamic/photodynamic therapies. Ferroptosis, cuproptosis, and disulfidptosis each possess distinct advantages and characteristics in the context of melanoma development, metastasis, and drug resistance. Leveraging both their common and unique mechanisms offers new perspectives for improving treatment outcomes.
Keywords: Melanoma, ferroptosis, cuproptosis, disulfidptosis, molecular interactions
Received: 13 Aug 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Li, Gao, Xing, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiangyang Zhang, xiangyang.zhang@tju.edu.cn
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