Special Issue "Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches 2.0"

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 28 February 2021.

Special Issue Editors

Dr. Cristina M. Failla
Website
Guest Editor
Istituto Dermopatico dell’Immacolata, IDI-IRCCS, 00167 Rome, Italy
Interests: dermal endothelial cell biology; physiological and pathological roles with a special focus on the expression of growth factor of the vascular endothelial growth factor family and their receptors; tumor angiogenesis in melanoma; inflammatory processes and tumor microenvironment
Special Issues and Collections in MDPI journals
Prof. Dr. Eleonora Candi
Website
Guest Editor
Department of Experimental Medicine, Università degli Studi di Roma “Tor Vergata”, Rome, Italy
Interests: the role of the transcription factor p63; homolog of p53; in epithelium development and tumor formation; p63-dependent metabolism changes in normal epithelia and in pathological conditions
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The publication of the first edition of this Special Issue has shown us that there is great interest in the field of skin cancer, and that many questions are still open and require additional investigation. As you know, skin cancer is the most common type of cancer, and its incidence is constantly increasing. Skin cancer comprises various skin tumor types, such as basal and squamous cell carcinomas, melanoma, Merkel cell carcinoma, cutaneous lymphomas, and other rare diseases, which present very different etiologies, incidences, therapeutic opportunities, and outcomes. Fortunately, research in recent years has brought novel and more effective therapeutic options, while others are foreseen in the near future. Nevertheless, open questions remain: which are the pathological drivers of skin cancers? What is the role of the skin microenvironment? Is there a role for the skin microbiota? Are there predictive biomarkers for immunotherapies? Are there molecular differences between skin cancer in young people and in adults? Is there a genetic predisposition to skin cancer? Is there a link between some therapeutic agents and skin cancer?

This second edition of the Special Issue intends to further highlight possible answers to these and other questions in the field, underlining research and clinical gaps and proposing opportunities for future studies. We welcome contributions focusing on molecular researches as well as more clinically-oriented researches to this new edition.

Dr. Cristina M. Failla
Prof. Dr. Eleonora Candi
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 papers will be 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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). 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

  • squamous cell carcinoma
  • basal cell carcinoma
  • melanoma
  • cutaneous lymphomas
  • tumor microenvironment
  • genetics

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Published Papers (3 papers)

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Research

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Open AccessArticle
Melanoma Cell Resistance to Vemurafenib Modifies Inter-Cellular Communication Signals
Biomedicines 2021, 9(1), 79; https://doi.org/10.3390/biomedicines9010079 - 15 Jan 2021
Abstract
The therapeutic success of BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) in BRAF-mutant melanoma is limited by the emergence of drug resistance, and several lines of evidence suggest that changes in the tumor microenvironment can play a pivotal role in acquired resistance. The [...] Read more.
The therapeutic success of BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) in BRAF-mutant melanoma is limited by the emergence of drug resistance, and several lines of evidence suggest that changes in the tumor microenvironment can play a pivotal role in acquired resistance. The present study focused on secretome profiling of melanoma cells sensitive or resistant to the BRAFi vemurafenib. Proteomic and cytokine/chemokine secretion analyses were performed in order to better understand the interplay between vemurafenib-resistant melanoma cells and the tumor microenvironment. We found that vemurafenib-resistant melanoma cells can influence dendritic cell (DC) maturation by modulating their activation and cytokine production. In particular, human DCs exposed to conditioned medium (CM) from vemurafenib-resistant melanoma cells produced higher levels of pro-inflammatory cytokines—that potentially facilitate melanoma growth—than DCs exposed to CM derived from parental drug-sensitive cells. Bioinformatic analysis performed on proteins identified by mass spectrometry in the culture medium from vemurafenib-sensitive and vemurafenib-resistant melanoma cells suggests a possible involvement of the proteasome pathway. Moreover, our data confirm that BRAFi-resistant cells display a more aggressive phenotype compared to parental ones, with a significantly increased production of interferon-γ, interleukin-8, vascular-endothelial growth factor, CD147/basigin, and metalloproteinase 2 (MMP-2). Plasma levels of CD147/basigin and MMP-2 were also measured before the start of therapy and at disease progression in a small group of melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib. A significant increment in CD147/basigin and MMP-2 was observed in all patients at the time of treatment failure, strengthening the hypothesis that CD147/basigin might play a role in BRAFi resistance. Full article
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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Open AccessArticle
Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes
Biomedicines 2020, 8(10), 404; https://doi.org/10.3390/biomedicines8100404 - 09 Oct 2020
Abstract
Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for [...] Read more.
Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for testing due to early melanoma (at <25 years) or the presence of multiple primary melanoma/melanoma and other cancer in their personal and/or family history. All patients were analyzed by panel next-generation sequencing targeting 217 genes in four groups: high-to-moderate melanoma risk genes, low melanoma risk genes, cancer syndrome genes, and other genes with an uncertain melanoma risk. Population frequencies were assessed in 1479 population-matched controls. Selected POT1 and CHEK2 variants were characterized by functional assays. Mutations in clinically relevant genes were significantly more frequent in melanoma patients than in controls (31/264; 11.7% vs. 58/1479; 3.9%; p = 2.0 × 10−6). A total of 9 patients (3.4%) carried mutations in high-to-moderate melanoma risk genes (CDKN2A, POT1, ACD) and 22 (8.3%) patients in other cancer syndrome genes (NBN, BRCA1/2, CHEK2, ATM, WRN, RB1). Mutations in high-to-moderate melanoma risk genes (OR = 52.2; 95%CI 6.6–413.1; p = 3.2 × 10−7) and in other cancer syndrome genes (OR = 2.3; 95%CI 1.4–3.8; p = 0.003) were significantly associated with melanoma risk. We found an increased potential to carry these mutations (OR = 2.9; 95%CI 1.2–6.8) in patients with double primary melanoma, melanoma and other primary cancer, but not in patients with early age at onset. The analysis revealed affected genes in Czech melanoma patients and identified individuals who may benefit from genetic testing and future surveillance management of mutation carriers. Full article
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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Review

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Open AccessReview
Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches
Biomedicines 2020, 8(11), 449; https://doi.org/10.3390/biomedicines8110449 - 23 Oct 2020
Abstract
Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor [...] Read more.
Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management. Full article
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches 2.0)
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