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Advances in Pathogenesis and Treatment of Skin Cancer (2nd Edition)
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Advances in Pathogenesis and Treatment of Skin Cancer (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: 30 September 2026 | Viewed by 5828

Editors

Dr. Enrica Flori

E-Mail Website
Guest Editor
IRCCS Istituto Dermatologico San Gallicano, 00144 Rome, Italy
Interests: skin inflammatory response; cross-talk among epidermal and dermal cells in pigmentary disorders; the role of nuclear receptors in the protective response against UV; skin cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Giorgia Cardinali

E-Mail Website
Guest Editor
San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy
Interests: skin; wound repair; growth factors and lipid signaling; hyperpigmentation; inflammatory
Special Issues, Collections and Topics in MDPI journals
Dr. Vittoria Maresca

E-Mail Website
Guest Editor
IRCCS Istituto Dermatologico San Gallicano, 00144 Rome, Italy
Interests: melanocytes; melanoma cells; alpha-MSH; MC1R; MC1R signal transduction pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Skin cancer includes various types of skin tumors, such as melanoma, basal cell and squamous cell carcinomas, cutaneous lymphomas, and other rare diseases, which have very different etiologies, incidences, therapeutic approaches, and outcomes. The incidence of skin cancers is steadily increasing, representing a major public health concern. In recent years, significant efforts have been made to develop effective therapeutic options, although several questions remain open. We welcome research contributions that focus on understanding the molecular pathways, biomarkers, oxidative stress, and skin microenvironment that are involved in the onset and progression of skin cancers. Exploring the mechanisms of etiopathogenesis may contribute to developing new and more effective therapeutic approaches for the prevention and treatment of skin cancer. Please note that pre-clinical and clinical contributions with biomolecular approaches will also be considered.

Dr. Enrica Flori
Dr. Giorgia Cardinali
Dr. Vittoria Maresca
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • melanoma
  • squamous cell carcinoma
  • basal cell carcinoma
  • tumor microenvironment
  • epithelial–mesenchymal transition (EMT) process
  • ultraviolet radiation
  • oxidative stress
  • bioactive modulators
  • signal transduction pathways

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Related Special Issue

Published Papers (3 papers)

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Research

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36 pages, 5917 KB  
Article
Epidermal PPARγ Signaling as a Suppressor of Toll-like Receptor-Mediated Inflammation and Fibrosis: Relevance to Cutaneous Squamous Cell Carcinoma
by Raymond L. Konger and Ethel Derr-Yellin
Int. J. Mol. Sci. 2026, 27(9), 4136; https://doi.org/10.3390/ijms27094136 - 5 May 2026
Viewed by 783
Abstract
Mice lacking epidermal Pparg (Pparg-/-epi) exhibit increased cutaneous carcinogenesis, while PPARγ signaling is reduced in actinic keratoses (AKs) and cutaneous squamous cell carcinomas (cSCCs). Using transcriptomic analysis, we now show that the top upregulated genes in Pparg-/-epi [...] Read more.
Mice lacking epidermal Pparg (Pparg-/-epi) exhibit increased cutaneous carcinogenesis, while PPARγ signaling is reduced in actinic keratoses (AKs) and cutaneous squamous cell carcinomas (cSCCs). Using transcriptomic analysis, we now show that the top upregulated genes in Pparg-/-epi mouse skin, human AKs and cSCCs encode multiple damage-associated molecular patterns (DAMPs) that are TLR4 ligands, while the TLR4 agonist lipopolysaccharide (LPS) is also predicted to be the top common activated upstream regulator in both Pparg-/-epi mouse skin and in tumor datasets. By single-cell sequencing, DAMP expression was particularly elevated in myeloid cells and myofibroblasts of Pparg-/-epi mice, and these cell types exhibit transcriptional changes consistent with TLR4 signaling. Myeloid cells also exhibited a loss of Pparg expression and activity. Transcriptional analysis of published LPS-treated macrophages also reveals a decrease in PPARγ activity. Fibroblasts from Pparg-/-epi mice included cells with a gene expression profile resembling myofibroblasts found in cancer and fibrotic diseases. This was accompanied by increased dermal fibrosis in aged mice and a transcriptomic profile that indicates a key role for both TLR4 and TGFβ signaling. These data suggest that loss of epidermal PPARγ may disrupt counterbalancing PPARγ–TLR4 signals, leading to chronic inflammation and fibrosis, hallmarks of cutaneous neoplasia. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Skin Cancer (2nd Edition))
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15 pages, 913 KB  
Article
Gray-Horse Melanoma—A Wolf in Sheep’s Clothing
by Daniela M. Brodesser, Karin Schlangen, Alexandro Rodríguez-Rojas, Benno Kuropka, Pavlos G. Doulidis, Sabine Brandt and Barbara Pratscher
Int. J. Mol. Sci. 2025, 26(14), 6620; https://doi.org/10.3390/ijms26146620 - 10 Jul 2025
Cited by 2 | Viewed by 2697
Abstract
Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique [...] Read more.
Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma “dormancy” in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Skin Cancer (2nd Edition))
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Review

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37 pages, 1127 KB  
Review
Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets
by Vittoria Maresca, Emanuela Bastonini, Giorgia Cardinali, Enrica Flori, Daniela Kovacs, Monica Ottaviani and Stefania Briganti
Int. J. Mol. Sci. 2026, 27(2), 1040; https://doi.org/10.3390/ijms27021040 - 20 Jan 2026
Viewed by 1738
Abstract
Melanoma is the deadliest form of skin cancer, characterized by high metastatic potential and intrinsic heterogeneity. In addition to genetic mutations such as BRAF^V600E^ and NRAS, lipid metabolic reprogramming has emerged as a critical factor in tumor progression and therapy resistance. Lipid metabolism [...] Read more.
Melanoma is the deadliest form of skin cancer, characterized by high metastatic potential and intrinsic heterogeneity. In addition to genetic mutations such as BRAF^V600E^ and NRAS, lipid metabolic reprogramming has emerged as a critical factor in tumor progression and therapy resistance. Lipid metabolism supports melanoma cell survival, phenotypic switching, immune evasion, and resistance to targeted therapies and immunotherapy, while also modulating susceptibility to ferroptosis. This review summarizes current knowledge on lipid dysregulation in melanoma, highlighting alterations in fatty acid synthesis, desaturation, uptake, storage, and oxidation, as well as changes in phospholipids, sphingolipids, cholesterol, and bioactive lipid mediators. These lipid pathways are tightly regulated by oncogenic signaling networks, including MAPK and PI3K–AKT–mTOR pathways, and are influenced by tumor microenvironmental stressors such as hypoxia and nutrient limitation. Advances in lipidomics technologies, particularly mass spectrometry-based approaches, have enabled comprehensive profiling of lipid alterations at bulk, spatial, and single-cell levels, offering new opportunities for biomarker discovery and therapeutic stratification. Targeting lipid metabolic vulnerabilities represents a promising strategy to improve melanoma diagnosis, prognosis, and treatment efficacy. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Skin Cancer (2nd Edition))
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