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Cancers
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Discoveries in Targeted Therapies for Melanoma: From Molecular Mechanisms to...
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Discoveries in Targeted Therapies for Melanoma: From Molecular Mechanisms to Therapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 1 November 2024 | Viewed by 800

Special Issue Editor

Dr. Georg Thomas Wondrak

E-Mail Website
Guest Editor
R. Ken Coit College of Pharmacy and UA Cancer Center, The University of Arizona, Tucson, AZ, USA
Interests: redox biology; cancer therapeutics; skin cancer; melanoma; molecular targets

Special Issue Information

Dear Colleagues,

The majority of skin cancer-related deaths is caused by malignant melanoma, a tumor originating from neural crest-derived melanocytes, and novel molecular strategies for the improved detection and treatment of melanoma are of substantial clinical significance. This Special Issue of Cancers, entitled ‘Discoveries in Targeted Therapy for Melanoma: From Molecular Mechanisms to Therapeutics’, aims at gathering original research and review papers on the current understanding of novel molecular mechanisms and therapeutic opportunities that might benefit melanoma patients in the near future.

Thank you for your research efforts. Please consider contributing to this Special Issue.

Dr. Georg Thomas Wondrak
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • malignant melanoma
  • cutaneous melanoma
  • uveal melanoma
  • drug resistance
  • targeted therapeutics
  • immune checkpoint inhibitors
  • targeted therapeutics
  • BRAF inhibitors
  • MEK inhibitors
  • drug discovery
  • molecular targets
  • melanoma diagnostics
  • precision medicine

Published Papers (1 paper)

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Research

15 pages, 2360 KiB  
Article
Targeted DNA Sequencing of Cutaneous Melanoma Identifies Prognostic and Predictive Alterations
by Alexandra M. Haugh, Robert C. Osorio, Rony A. Francois, Michael E. Tawil, Katy K. Tsai, Michael Tetzlaff, Adil Daud and Harish N. Vasudevan
Cancers 2024, 16(7), 1347; https://doi.org/10.3390/cancers16071347 - 29 Mar 2024
Viewed by 602
Abstract
Background: Cutaneous melanoma (CM) can be molecularly classified into four groups: BRAF mutant, NRAS mutant, NF1 mutant and triple wild-type (TWT) tumors lacking any of these three alterations. In the era of immune checkpoint inhibition (ICI) and targeted molecular therapy, the clinical significance [...] Read more.
Background: Cutaneous melanoma (CM) can be molecularly classified into four groups: BRAF mutant, NRAS mutant, NF1 mutant and triple wild-type (TWT) tumors lacking any of these three alterations. In the era of immune checkpoint inhibition (ICI) and targeted molecular therapy, the clinical significance of these groups remains unclear. Here, we integrate targeted DNA sequencing with comprehensive clinical follow-up in CM patients. Methods: This was a retrospective cohort study that assessed clinical and molecular features from patients with localized or metastatic CM who underwent targeted next-generation sequencing as part of routine clinical care. A total of 254 patients with CM who had a CLIA-certified targeted sequencing assay performed on their tumor tissue were included. Results: Of the 254 patients with cutaneous melanoma, 77 were BRAF mutant (30.3%), 77 were NRAS mutant (30.3%), 47 were NF1 mutant (18.5%), 33 were TWT (13.0%) and the remaining 20 (7.9%) carried mutations in multiple driver genes (BRAF/NRAS/NF1 co-mutated). The majority of this co-mutation group carried mutations in NF1 (n = 19 or 90%) with co-occurring mutations in BRAF or NRAS, often with a weaker oncogenic variant. Consistently, NF1 mutant tumors harbored numerous significantly co-altered genes compared to BRAF or NRAS mutant tumors. The majority of TWT tumors (n = 29, 87.9%) harbor a pathogenic mutation within a known Ras/MAPK signaling pathway component. Of the 154 cases with available TMB data, the median TMB was 20 (range 0.7–266 mutations/Mb). A total of 14 cases (9.1%) were classified as having a low TMB (≤5 mutations/Mb), 64 of 154 (41.6%) had an intermediate TMB (>5 and ≤20 mutations/Mb), 40 of 154 (26.0%) had a high TMB (>20 and ≤50 mutations/Mb) and 36 of 154 (23.4%) were classified as having a very high TMB (>50 mutations/Mb). NRAS mutant melanoma demonstrated significantly decreased overall survival on multivariable analysis (HR for death 2.95, 95% CI 1.13–7.69, p = 0.027, log-rank test) compared with other TCGA molecular subgroups. Of the 116 patients in our cohort with available treatment data, 36 received a combination of dual ICI with anti-CTLA4 and anti-PD1 inhibition as first-line therapy. Elevated TMB was associated with significantly longer progression-free survival following dual-agent ICI (HR 0.26, 95% CI 0.07–0.90, p = 0.033, log-rank test). Conclusions: NRAS mutation in CMs correlated with significantly worse overall survival. Elevated TMB was associated with increased progression-free survival for patients treated with a combination of dual ICI, supporting the potential utility of TMB as a predictive biomarker for ICI response in melanoma. Full article
(This article belongs to the Special Issue Discoveries in Targeted Therapies for Melanoma: From Molecular Mechanisms to Therapeutics)
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