Melanoma and Redox Dynamics: A Crucial Tug-of-War in Tumor Onset and in Therapy Response

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 852

Special Issue Editors


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Guest Editor
Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy
Interests: neuroblastoma; MYC amplification; cancer stemness; drug resistance; protein kinase C; oxidative stress; lipoperoxidation; apoptosis
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Guest Editor
Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy
Interests: chemoresistance; cancer cell metabolism; stress adaptative cell response; cell death; redox homeostasis; redox signalling; antioxidants; glutathione
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cutaneous melanoma is among the best-known tumors induced by overproduction of Reactive Oxygen Species (ROS). Oxidative stress and redox homeostasis are involved in the onset of melanoma and its therapy resistance: oxidants promote cancer initiation and also counteract tumor spread, while antioxidants are involved in metastatization. In addition, melanoma adapt to oxidative conditions through the reprogramming of metabolism and the activation of antioxidant defenses and progressively acquires malignancy and metastatic potential.

Therefore, given the incidence and development of therapy resistance, identifying new melanoma "redox vulnerabilities" that could become effective therapeutic targets is a pressing priority. To achieve this goal, we must broaden our perspective and consider all the "competitors" participating in this "redox game". In particular, it is necessary to consider the intricate network of interactions between ROS, redox-modulated signaling pathways, redox-related transcription factors, mitochondria, cell response, as well as to understand the complexity of metabolic reprogramming and redox adaptive mechanisms.

From a therapeutic point of view, antioxidants have been found to be useful as chemopreventive agents, while oxidants may function as chemotherapeutics. Furthermore, natural compounds may act as adjuvants capable of reducing the side effects of conventional therapies, overcoming therapy resistance, and improving the survival rate of melanoma patients.

Based on these considerations, this Special Issue is dedicated to original articles and reviews focused on identifying novel redox sensitive targets to counteract melanoma progression and therapeutic resistance. Furthermore, contributions dealing with innovative experimental methods aimed at better understanding melanoma biology, as well as precision medicine approaches employing the combination of the conventional therapy with a redox-centered targeted therapy, are welcome.

Prof. Dr. Cinzia Domenicotti
Dr. Barbara Marengo
Guest Editors

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Keywords

  • melanoma
  • redox homeostasis
  • ROS
  • antioxidants
  • therapy resistance
  • cancer metabolism
  • mitochondria
  • epigenetic changes
  • innovative therapeutic and experimental approaches

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Published Papers (1 paper)

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Research

19 pages, 2647 KB  
Article
Adipocyte-Derived Extracellular Vesicles Endow Melanoma Cells with Stem-like Traits via PGC-1α–Mediated Mitochondrial Reprogramming
by Gaia Giannitti, Sara Marchesi, Riccardo Garavaglia, Ivan Preosto, Emanuela Carollo, Patrizia Sartori and Fabrizio Fontana
Antioxidants 2026, 15(3), 333; https://doi.org/10.3390/antiox15030333 - 6 Mar 2026
Viewed by 640
Abstract
Melanoma is an aggressive cancer characterized by a rapid metastatic process. Thus, understanding the mechanisms underlying its progression is urgently needed to improve patient outcomes. In this regard, there is consistent evidence of a tumor-sustaining crosstalk between melanoma and subcutaneous adipose tissue; however, [...] Read more.
Melanoma is an aggressive cancer characterized by a rapid metastatic process. Thus, understanding the mechanisms underlying its progression is urgently needed to improve patient outcomes. In this regard, there is consistent evidence of a tumor-sustaining crosstalk between melanoma and subcutaneous adipose tissue; however, the role of extracellular vesicles (EVs) in this communication still needs to be clarified. We demonstrated that the EVs derived from adipocytes did not alter melanoma cell proliferation but significantly promoted tumor cell migration and invasion by determining an enrichment in mesenchymal markers, such as N-cadherin and vimentin. In particular, these changes were accompanied by the transition towards a stem-like phenotype, characterized by enhanced spherogenic ability and ABCG2 upregulation; interestingly, this led to a reduced in vitro response to the BRAF inhibitor vemurafenib. Mechanistically, an increase in PGC-1α expression was found, resulting in higher mitochondrial mass and activity, ATP synthesis, and ROS overproduction; of note, treatment of melanoma cells with SR-18292 and XCT790, two inactivators of mitochondrial biogenesis, and N-acetylcysteine, a ROS scavenger, successfully counteracted the above EV-related effects, suggesting that mitochondrial function could be targeted to suppress the vesicular interactions between adipose tissue and melanoma. Taken together, these results highlight the crucial role played by EVs in melanoma stroma, pointing out the ability of adipocyte-derived vesicles to sustain cancer aggressiveness via PGC-1α–dependent mitochondrial reprogramming. Full article
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