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Melanoma: Molecular Mechanism and Therapy, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 751

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Guest Editor
Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Interests: human malignant melanoma; genomic alterations; gene expression alterations; chromosome copy number alterations; array CGH; FISH
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Special Issue Information

Dear Colleagues,

This Special Issue builds on the success of our previous edition, Melanoma: Molecular Mechanisms and Therapy, via continuing to explore the latest advances in understanding and treating one of the most aggressive forms of skin cancer.

Melanoma is characterized by high metastatic potential, presenting a major clinical challenge, especially in advanced stages. While early-stage melanoma has a favorable prognosis—with five-year survival rates exceeding 98%— this rate drops dramatically to approximately 17% in patients with distant metastases. Over the past decade, significant progress has been made in the development of targeted therapies and immunotherapies, which have improved clinical outcomes for patients with advanced and metastatic disease. Despite these innovations, the treatment of melanoma with distant metastases remains a complex clinical challenge. The molecular mechanisms underlying melanoma progression, metastasis, and therapy resistance are complex and not yet fully elucidated. Although therapies targeting key signaling pathways (e.g., BRAF and MEK inhibitors) and immune checkpoints demonstrate initial efficacy, resistance frequently develops, often driven by the molecular heterogeneity and plasticity of melanoma cells. This underscores the need for deeper insights into the pathways governing tumor evolution and therapeutic escape.

This Special Issue aims to highlight recent advances in our understanding of the molecular basis of melanoma development, metastasis, and resistance to therapy. We welcome original research articles, reviews, and short communications that investigate molecular drivers of disease progression, mechanisms of drug resistance, novel therapeutic targets, and biomarkers predictive of treatment response. Submissions that provide mechanistic insights with potential translational relevance are particularly encouraged.

Prof. Dr. Balázs Margit
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • melanoma progression
  • melanoma metastasis
  • molecular background
  • targeted therapies
  • immunotherapy
  • acquired drug resistance
  • prognostic and predictive markers
  • therapeutic targets

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Related Special Issue

Published Papers (2 papers)

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Research

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9 pages, 629 KB  
Communication
Circulating Calprotectin Distinguishes Metastatic Melanoma and Predicts Liver Metastasis
by István Szász, Viktória Koroknai, Tünde Várvölgyi, Gabriella Emri, Imre Lőrinc Szabó and Margit Balázs
Int. J. Mol. Sci. 2025, 26(16), 8028; https://doi.org/10.3390/ijms26168028 - 20 Aug 2025
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Abstract
Calprotectin, a heterodimer of the S100A8 and S100A9 proteins, has been implicated in cancer-related inflammation and metastasis. Its role in melanoma progression, particularly in organ-specific metastasis, remains underexplored. In this retrospective study, plasma calprotectin levels were measured in 201 individuals, including healthy controls [...] Read more.
Calprotectin, a heterodimer of the S100A8 and S100A9 proteins, has been implicated in cancer-related inflammation and metastasis. Its role in melanoma progression, particularly in organ-specific metastasis, remains underexplored. In this retrospective study, plasma calprotectin levels were measured in 201 individuals, including healthy controls (n = 22), melanoma patients without evidence of metastasis (n = 71), and patients with metastatic melanoma (n = 108). Calprotectin concentrations were determined using the ELISA assay. Receiver operating characteristic (ROC) curve analyses were used to evaluate its diagnostic value, both alone and in combination with established biomarkers S100B and LDH. Plasma calprotectin levels were significantly elevated in patients with metastatic melanoma compared to non-metastatic patients (p < 0.001). Calprotectin showed moderate diagnostic value (AUC = 0.672), which improved to 0.755 when combined with S100B and LDH. Organ-specific analysis revealed that patients with liver metastases exhibited the highest calprotectin concentrations, with good discriminatory power (AUC = 0.710). No significant association was found between calprotectin levels and the type of metastasis identified (lymphatic vs. hematogenous). Logistic regression analysis showed that calprotectin levels above 2728 ng/mL were associated with a 7.4-fold increased risk of liver metastasis. Calprotectin is a promising blood-based biomarker that may enhance the detection of metastatic melanoma, particularly in cases with liver involvement. These findings suggest that calprotectin could be integrated into multivariable prediction models to improve risk stratification in clinical practice. Full article
(This article belongs to the Special Issue Melanoma: Molecular Mechanism and Therapy, 2nd Edition)
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13 pages, 1135 KB  
Brief Report
Assessing Determinants of Response to PARP Inhibition in Germline ATM Mutant Melanoma
by Eleonora Allavena, Michela Croce, Bruna Dalmasso, Cecilia Profumo, Valentina Rigo, Virginia Andreotti, Irene Vanni, Benedetta Pellegrino, Antonino Musolino, Nicoletta Campanini, William Bruno, Luca Mastracci, Gabriele Zoppoli, Enrica Teresa Tanda, Francesco Spagnolo, Paola Ghiorzo and Lorenza Pastorino
Int. J. Mol. Sci. 2025, 26(15), 7420; https://doi.org/10.3390/ijms26157420 - 1 Aug 2025
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Abstract
The ataxia–telangiectasia-mutated (ATM) protein plays a crucial role in the DNA damage response, particularly in the homologous recombination (HR) pathway. This study aimed to assess the impact of deleterious ATM variants on homologous recombination deficiency (HRD) and response to PARP inhibitors (PARPi) in [...] Read more.
The ataxia–telangiectasia-mutated (ATM) protein plays a crucial role in the DNA damage response, particularly in the homologous recombination (HR) pathway. This study aimed to assess the impact of deleterious ATM variants on homologous recombination deficiency (HRD) and response to PARP inhibitors (PARPi) in melanoma patients, using a cell line established from melanoma tissue of a patient carrying the c.5979_5983del germline ATM variant. Despite proven loss of heterozygosity, lack of ATM activation, and HRD, our model did not show sensitivity to PARPi. We assessed the potential contribution of the Schlafen family member 11 (SLFN11) helicase, whose expression is inversely correlated with PARPi sensitivity in other cancers, to the observed resistance. The ATM mutant cell line lacked SLFN11 expression and featured hypermethylation-mediated silencing of the SLFN11 promoter. While sensitive to the ATR inhibitor (ATRi), the addition of ATRi to PARPi was unable to overcome the resistance. Our findings suggest that ATM mutational status and HRD alone do not adequately account for variations in sensitivity to PARPi in our model. A comprehensive approach is essential for optimizing the exploitation of DNA repair defects and ultimately improving clinical outcomes for melanoma patients. Full article
(This article belongs to the Special Issue Melanoma: Molecular Mechanism and Therapy, 2nd Edition)
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