Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
Skin Cancer: From Molecular Pathophysiology to Novel Treatment
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Skin Cancer: From Molecular Pathophysiology to Novel Treatment

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: 20 June 2026 | Viewed by 4999

Special Issue Editor

Prof. Dr. Soon-Hyo Kwon

E-Mail Website
Guest Editor
Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Republic of Korea
Interests: solar lentigo; RNA-seq data; inflammation; oxidative stress; dermatology; skin; photoaging

Special Issue Information

Dear Colleagues,

We invite researchers to submit original studies and reviews focusing on the molecular mechanisms underlying skin cancer, including genetic mutations, epigenetic modifications, and dysregulated signaling pathways. Special emphasis is placed on tumor microenvironment interactions, immune evasion, and resistance mechanisms. We particularly welcome studies identifying novel molecular targets and developing innovative therapeutic strategies, such as targeted therapies, immunotherapies, and nanomedicine-based approaches. Additionally, research on biomarkers for early detection, prognosis, and treatment response is encouraged.

This collection aims to bridge fundamental molecular research with translational and clinical applications, providing insights into next-generation skin cancer therapies. Contributions from various disciplines, including molecular biology, bioinformatics, and pharmaceutical sciences, are highly encouraged.

By bringing together cutting-edge research, we hope to advance our understanding of skin cancer pathophysiology and foster the development of more effective treatments. Submit your work to contribute to this growing field and shape the future of skin cancer therapy.

Prof. Dr. Soon-Hyo Kwon
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 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-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.

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

  • basal cell carcinoma
  • malignant melanoma
  • molecular genetics
  • epigenetics
  • signaling pathways
  • tumor microenvironment
  • tumor resistance
  • biomarkers
  • molecular target
  • multiomics
  • genomics
  • transcriptomics
  • proteomics
  • metabolomics
  • skin cancer
  • squamous cell carcinoma

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

24 pages, 2357 KB  
Article
Aberrant Activation of the Hedgehog Pathway in Cutaneous Melanoma: Therapeutic Potential of Pharmacological Inhibitors
by Federica Papaccio, Daniela Kovacs, Ramona Marrapodi, Silvia Caputo, Emilia Migliano, Elisa Melucci, Stefano Scalera, Carlo Cota, Marcello Maugeri-Saccà and Barbara Bellei
Int. J. Mol. Sci. 2026, 27(2), 762; https://doi.org/10.3390/ijms27020762 - 12 Jan 2026
Viewed by 599
Abstract
Cutaneous melanoma is a highly aggressive skin cancer prone to relapse and metastasis. Surgery is often curative when combined with early screening and prevention. However, in recurrent or advanced disease, the development of new targeted and immune therapies has demonstrated promising clinical outcomes, [...] Read more.
Cutaneous melanoma is a highly aggressive skin cancer prone to relapse and metastasis. Surgery is often curative when combined with early screening and prevention. However, in recurrent or advanced disease, the development of new targeted and immune therapies has demonstrated promising clinical outcomes, although the acquisition of resistance limits their effectiveness. Thus, new therapeutic approaches are needed. Emerging data indicate that the Hedgehog (Hh) pathway, which is essential for embryonic development, is aberrantly reactivated in melanoma and may represent a promising therapeutic target. Here, we demonstrate its chronic up-modulation in a panel of patient-derived cell lines and, by investigating the underlying molecular mechanisms, we excluded mutations in the principal components of the pathway. We observed reduced PTCH1 and SUFU repressors expression and GLI2 upregulation as common melanoma features. At the same time, copious SHH release, the principal PTCH1 ligand, evidenced autocrine Hh signaling activation. Consistently, a tendency of greater level of this factor resulted higher in the blood of patients compared to controls, confirming the relevance of ligand-dependent trigger in melanoma. The therapeutic potential of inhibiting the Hh pathway is highlighted by the reduced proliferation and migration observed in the presence of clinically approved pharmacological Hh antagonists. Profiling inflammatory mediators revealed significant modulation upon treatment with SMO inhibitors, possibly affecting chemotactic and immune functions. Collectively, these findings provide deeper insight into the role of the Hh pathway in melanoma and support the potential repurposing of Hh inhibitors as therapeutic agents for melanoma. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Pathophysiology to Novel Treatment)
►▼ Show Figures

Figure 1

19 pages, 1145 KB  
Article
Checkpoint Blockade Efficacy in Uveal Melanoma Is Linked to Tumor Immunity, CD28, and CCL8
by Elias A. T. Koch, Renato Liguori, Alejandro Afonso Castro, Stefan Schliep, Anne Petzold, Anja Wessely, Waltraud Fröhlich, Fulvia Ferrazzi, Julio Vera, Markus Eckstein, Carola Berking and Markus V. Heppt
Int. J. Mol. Sci. 2025, 26(20), 9964; https://doi.org/10.3390/ijms26209964 - 13 Oct 2025
Cited by 1 | Viewed by 1279
Abstract
For patients with metastatic uveal melanoma (UM), tebentafusp is currently the only systemic therapy approved by the EMA and FDA, but its use is limited to HLA-A*02:01-positive individuals. Immune checkpoint blockade (ICB) represents another option, though only a small subgroup of patients benefits, [...] Read more.
For patients with metastatic uveal melanoma (UM), tebentafusp is currently the only systemic therapy approved by the EMA and FDA, but its use is limited to HLA-A*02:01-positive individuals. Immune checkpoint blockade (ICB) represents another option, though only a small subgroup of patients benefits, and no reliable predictive biomarkers are available to date. The aim of this study was therefore to identify parameters associated with favorable ICB response. Tumor samples and clinical data from 30 patients were analyzed. Group A (n = 16) showed clinical benefit, while Group B (n = 14) experienced disease progression. NanoString® analyses revealed 258 upregulated genes in Group A, including IDO1, CD28, and CCL8. The enriched pathways were predominantly linked to immune activation, leukocyte adhesion, and responses to external stimuli. Immunohistochemistry confirmed significantly higher CD28 expression on infiltrating immune cells in Group A, while a machine learning approach identified CCL8 as a predictive marker with ~78% accuracy. Overall survival differed significantly between the groups. These findings indicate that patients responding to ICB display tumors with enhanced immune activation. CD28 and CCL8 emerged as promising candidates and should be validated in prospective studies to determine their clinical utility. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Pathophysiology to Novel Treatment)
►▼ Show Figures

Figure 1

13 pages, 1527 KB  
Article
Ethnic-Specific and UV-Independent Mutational Signatures of Basal Cell Carcinoma in Koreans
by Ye-Ah Kim, Seokho Myung, Yueun Choi, Junghyun Kim, Yoonsung Lee, Kiwon Lee, Bark-Lynn Lew, Man S. Kim and Soon-Hyo Kwon
Int. J. Mol. Sci. 2025, 26(14), 6941; https://doi.org/10.3390/ijms26146941 - 19 Jul 2025
Cited by 1 | Viewed by 1469
Abstract
Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from [...] Read more.
Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Pathophysiology to Novel Treatment)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

20 pages, 553 KB  
Review
Surgical Management of Stage IV Melanoma: Clinical, Molecular, and Therapeutic Considerations
by Ifeanyi K. Uche and John M. Lyons III
Int. J. Mol. Sci. 2026, 27(5), 2327; https://doi.org/10.3390/ijms27052327 - 2 Mar 2026
Viewed by 471
Abstract
Despite major advances in systemic therapy, surgery still plays a valuable role in the management of metastatic melanoma. This review summarizes the historical evolution of surgical management, outlines the traditional clinical risk factors, and examines biochemical, molecular, and mutational factors that impact melanoma [...] Read more.
Despite major advances in systemic therapy, surgery still plays a valuable role in the management of metastatic melanoma. This review summarizes the historical evolution of surgical management, outlines the traditional clinical risk factors, and examines biochemical, molecular, and mutational factors that impact melanoma tumor biology. Emerging tools such as predictive biomarker assays, gene expression profiling, and circulating tumor DNA are discussed in the context of patient selection. Finally, we consider contemporary indications for surgery, the management of oligoprogression, sequence of treatment, and optimal timing of resection while highlighting how operative intervention integrates with modern melanoma care. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Pathophysiology to Novel Treatment)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

6 pages, 612 KB  
Case Report
Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling
by Federica Papaccio, Ramona Marrapodi, Laura Eibenschutz, Andrea D’Arino, Silvia Caputo, Alberto Marini, Simona Scano, Arianna Presaghi, Carlo Cota, Elisa Melucci, Stefano Scalera, Emilia Migliano, Marcello Maugeri-Saccà, Pasquale Frascione and Barbara Bellei
Int. J. Mol. Sci. 2026, 27(1), 68; https://doi.org/10.3390/ijms27010068 - 21 Dec 2025
Cited by 1 | Viewed by 678
Abstract
Basal cell carcinoma (BCC) is the most common skin cancer, predominantly affecting sun-exposed areas. It typically grows slowly and rarely metastasizes, though untreated cases can cause significant tissue destruction and morbidity. Its pathogenesis primarily involves dysregulation of the Hedgehog (HH) signaling pathway, mainly [...] Read more.
Basal cell carcinoma (BCC) is the most common skin cancer, predominantly affecting sun-exposed areas. It typically grows slowly and rarely metastasizes, though untreated cases can cause significant tissue destruction and morbidity. Its pathogenesis primarily involves dysregulation of the Hedgehog (HH) signaling pathway, mainly through mutations in PTCH1 or SMO genes, leading to chronic activation of downstream GLI transcription factors. Accordingly, current targeted therapies for locally advanced, unresectable, or metastatic BCC focus on SMO inhibition, using orally administered drugs such as vismodegib and sonidegib. Although these therapies have shown success, many patients develop resistance, with about 50% harboring mutated SMO. In numerous cases, genetic determinants (sometimes pre-existing) of resistance remain unidentified, complicating patient management. Here, we report a case of a 58-year-old female with advanced BCC who initially exhibited a favorable response to sonidegib but developed resistance after approximately one year. This resistance was not attributable to the acquired mutations in SMO but rather to intra-tumor heterogeneity and additional mutations in critical driver genes, including TP53, APC, FGFR1 and NOTCH1, which likely enable HH pathway inhibition. To our knowledge, this is the first report documenting a sonidegib resistance mechanism in BCC that is independent of HH pathway mutations. This case highlights the complexity of resistance mechanisms to HH inhibitors and underscores the critical need for comprehensive molecular tumor profiling prior to initiating targeted therapy. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Pathophysiology to Novel Treatment)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop