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Cancers
Special Issues
Advances in Melanoma Treatments: Molecular Targeted Therapies, Immunotherapies and Vaccines
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Advances in Melanoma Treatments: Molecular Targeted Therapies, Immunotherapies and Vaccines

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

Deadline for manuscript submissions: 20 September 2024 | Viewed by 1516

Special Issue Editors

Dr. Gagan Chhabra

E-Mail Website
Guest Editor
Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA
Interests: melanoma; novel molecular targets; targeted therapy
Dr. Chandra Singh

E-Mail Website
Guest Editor
Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA
Interests: Melanoma; novel molecular targets; targeted therapy
Dr. Ichwaku Rastogi

E-Mail Website
Guest Editor
UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA
Interests: cancer vaccines; immunotherapy

Special Issue Information

Dear Colleagues,

Several therapies are currently being used for melanoma treatment, the most recent one being immunotherapy. Despite this, no treatment is fully effective at achieving long-term remission for melanoma patients. Therefore, the development of new therapeutic strategies including novel molecular targeted therapies, immune checkpoint therapies and vaccines are required to combat this deadly skin neoplasm. The use of vaccine therapy in melanoma is the most advanced and natural way of training the immune system of the patient to identify and lyse the cancer cells specifically, and in some cases even prevent the recurrence of the disease. Moreover, the use of immune checkpoint inhibitors can promote the activation of pre-existing antigen-specific CD8 T cells to combat cancer progression. On the other hand, the use of molecularly targeted therapies has also demonstrated promise in slowing/preventing the disease. Given the recent success of these therapies, it may be worth exploring their specific combinations given together or in sequence to improve overall efficacies. Several research groups are currently evaluating these approaches for the treatment of melanoma and many of these strategies are being tested in early-phase clinical trials. This Special Issue will focus on discussing the recent advances in the field as well as commenting on the future implications of these findings. Through this, we plan to emphasize the knowledge gaps that currently exist and address the potential ways that can lead to the improvement of current therapeutic approaches against melanoma.

Dr. Gagan Chhabra
Dr. Chandra Singh
Dr. Ichwaku Rastogi
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 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

  • melanoma
  • molecular targets
  • DNA vaccines
  • RNA vaccines
  • peptide vaccines
  • virus/bacteria-based vaccines
  • protein vaccines
  • antigen-loaded cellular vaccines
  • immune checkpoints
  • immunotherapies

Published Papers (1 paper)

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Research

23 pages, 7419 KiB  
Article
Exploring the In Vitro and In Vivo Therapeutic Potential of BRAF and MEK Inhibitor Combination in NRAS-Mutated Melanoma
by Heike Niessner, Anna Hüsch, Corinna Kosnopfel, Matthias Meinhardt, Dana Westphal, Friedegund Meier, Bastian Schilling and Tobias Sinnberg
Cancers 2023, 15(23), 5521; https://doi.org/10.3390/cancers15235521 - 22 Nov 2023
Viewed by 1173
Abstract
Introduction: Patients with NRAS-mutant metastatic melanoma often have an aggressive disease requiring a fast-acting, effective therapy. The MEK inhibitor binimetinib shows an overall response rate of 15% in patients with NRAS-mutant melanoma, providing a backbone for combination strategies. Our previous studies demonstrated that [...] Read more.
Introduction: Patients with NRAS-mutant metastatic melanoma often have an aggressive disease requiring a fast-acting, effective therapy. The MEK inhibitor binimetinib shows an overall response rate of 15% in patients with NRAS-mutant melanoma, providing a backbone for combination strategies. Our previous studies demonstrated that in NRAS-mutant melanoma, the antitumor activity of the MEK inhibitor binimetinib was significantly potentiated by the BRAFV600E/K inhibitor encorafenib through the induction of ER stress, leading to melanoma cell death by apoptotic mechanisms. Encorafenib combined with binimetinib was well tolerated in a phase III trial showing potent antitumor activity in BRAF-mutant melanoma, making a rapid evaluation in NRAS-mutant melanoma imminently feasible. These data provide a mechanistic rationale for the evaluation of binimetinib combined with encorafenib in preclinical and clinical studies on NRAS-mutant metastatic melanoma. Methods: The combination of BRAFi plus MEKi was tested in a monolayer culture of patient-derived cell lines and in corresponding patient-derived tissue slice cultures of NRAS-mutant melanoma. To investigate the treatment in vivo, NSG (NOD. Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice were subcutaneously injected with three different BRAF wild-type melanoma models harboring oncogenic NRAS mutations and treated orally with encorafenib (6 mg/kg body weight, daily) with or without binimetinib (8 mg/kg body weight, twice daily). In parallel, an individual healing attempt was carried out by treating one patient with an NRAS-mutated tumor. Results: Encorafenib was able to enhance the inhibitory effect on cell growth of binimetinib only in the cell line SKMel147 in vitro. It failed to enhance the apoptotic effect found in two other NRAS-mutated cell lines. Encorafenib led to a hyperactivation of ERK which could be reduced with the combinational treatment. In two of the three patient-derived tissue slice culture models of NRAS-mutant melanomas, a slight tendency of a combinatorial effect was seen which was not significant. Encorafenib showed a slight induction of the ER stress genes ATF4, CHOP, and NUPR1. The combinational treatment was able to enhance this effect, but not significantly. In the mouse model, the combination therapy of encorafenib with binimetinib resulted in reduced tumor growth compared to the control and encorafenib groups; however, the best effect in terms of tumor growth inhibition was measured in the binimetinib therapy group. The therapy showed no effect in an individual healing attempt for a patient suffering from metastatic, therapy-refractory NRAS-mutated melanoma. Conclusion: In in vitro and ex vivo settings, the combination therapy was observed to elicit a response; however, it did not amplify the efficacy observed with binimetinib alone, whereas in a patient, the combinational treatment remained ineffective. The preclinical in vivo data showed no increased combinatorial effect. However, the in vivo effect of binimetinib as monotherapy was unexpectedly high in the tested regimen. Nevertheless, binimetinib proved to be advantageous in the treatment of melanoma in vivo and led to high rates of apoptosis in vitro; hence, it still seems to be a good base for combination with other substances in the treatment of patients with NRAS-mutant melanoma. Full article
(This article belongs to the Special Issue Advances in Melanoma Treatments: Molecular Targeted Therapies, Immunotherapies and Vaccines)
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