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Biomolecules
Special Issues
Advances in Melanoma Targeted Therapy
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Advances in Melanoma Targeted Therapy

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 9872

Special Issue Editor

Dr. Dmitriy Minond

E-Mail Website
Guest Editor
College of Pharmacy and Rumbaugh Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL 33314, USA
Interests: drug screening; anti-cancer drug design and discovery; drug target development; small-molecule drug discovery; cancer biology

Special Issue Information

Dear Colleagues,

Despite the advances in melanoma therapy in recent years, there is still a pressing need for novel approaches and targets. The current treatments for melanoma have many limitations, including low response rates, a lack of targeted therapies for “triple-wide type” and NRAS mutant melanoma, and drug resistance, all of which necessitate the discovery of new agents and targets for melanoma.

In this Special Issue, we aim to publish the most recent developments in targeted therapies for melanoma.

We would like to invite you to contribute research and review manuscripts that report on novel molecules (small and large) that are active against melanoma and novel targets.

We look forward to reading your contributions.

Dr. Dmitriy Minond
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. Biomolecules 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 2700 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
  • drug discovery
  • new targets
  • target discovery

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

Published Papers (3 papers)

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Research

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19 pages, 2778 KB  
Article
Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma
by Alexei A. Maslov, Nicholas H. Trageser, Julia V. Kichina, Haya Elamir, Evelyn Gardner, Frances Teaman, Vera Vishwanath, Scott M. Dugas, Johanna Heid, Alexander Y. Maslov, Henry G. Withers, Anna Bianchi-Smiraglia, Katerina I. Leonova, Mikhail A. Nikiforov and Eugene S. Kandel
Biomolecules 2025, 15(10), 1425; https://doi.org/10.3390/biom15101425 - 7 Oct 2025
Viewed by 1104
Abstract
Uveal melanoma is a melanocyte-derived malignancy of the eye with a high propensity for liver metastasis. Metastatic uveal melanoma is associated with high mortality and is poorly responsive to currently available therapies. Most uveal melanoma cases are driven by activating mutations in GNAQ [...] Read more.
Uveal melanoma is a melanocyte-derived malignancy of the eye with a high propensity for liver metastasis. Metastatic uveal melanoma is associated with high mortality and is poorly responsive to currently available therapies. Most uveal melanoma cases are driven by activating mutations in GNAQ and GNA11 genes, which convey oncogenic signaling through the mitogen-activated protein kinase (MAPK) pathway. Despite promising early results, safe doses of pharmacological inhibitors of the MAPK cascade failed to effectively control uveal melanoma in human trials. Considering the role of the RAC/PAK signaling axis as a co-regulator of the MAPK cascade, we set forth to investigate whether the efficacy of MAPK cascade inhibitors in pre-clinical models may be enhanced by direct inhibition of RAC and PAK proteins, or by indirect control of RAC via inhibition of guanylate biosynthesis. We observed that pharmacological inhibition of RAC, PAK and the key guanylate biosynthesis enzyme IMPDH significantly synergized with various inhibitors of the MAPK cascade in suppressing oncogenic signaling and the growth of uveal melanoma cells. In a mouse model, the addition of an IMPDH inhibitor to the treatment regimen significantly enhanced the ability of a MAPK cascade inhibitor to improve the survival of tumor-bearing animals. Targeting of the RAC/PAK axis provides a new strategy to increase the efficacy of targeted therapies in uveal melanoma. While RAC and PAK inhibitors are still undergoing pre-clinical development, clinically available inhibitors of IMPDH offer an opportunity to test the efficacy of this novel synergistic combination in the context of human disease. Full article
(This article belongs to the Special Issue Advances in Melanoma Targeted Therapy)
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14 pages, 2675 KB  
Article
Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
by Sadeeshkumar Velayutham, Ryan Seerattan, Maab Sultan, Trisha Seal, Samaya Danthurthy, Baskaran Chinnappan, Jessica Landi, Kaitlyn Pearl, Aveta Singh, Keiran S. M. Smalley, Julia Zaias, Jun Yong Choi and Dmitriy Minond
Biomolecules 2023, 13(9), 1276; https://doi.org/10.3390/biom13091276 - 22 Aug 2023
Cited by 6 | Viewed by 4633
Abstract
Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were [...] Read more.
Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to assess the efficacy of these compounds by testing them in A375 cell-line xenograft in nude athymic mice. Animals were randomized into four groups (n = 12/group): 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 thrice a week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results demonstrate the therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2. Full article
(This article belongs to the Special Issue Advances in Melanoma Targeted Therapy)
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9 pages, 1567 KB  
Brief Report
In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2
by Sadeeshkumar Velayutham, Trisha Seal, Samaya Danthurthy, Julia Zaias, Keiran S. M. Smalley and Dmitriy Minond
Biomolecules 2023, 13(2), 349; https://doi.org/10.3390/biom13020349 - 10 Feb 2023
Cited by 5 | Viewed by 3170
Abstract
Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side [...] Read more.
Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50 mg/kg/day via subcutaneous injections, and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, the effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the body weight, blood cell count, blood chemistry, or organs of the mice following the compound treatment. The results show that our compounds, 2155-14 and 2155-18, are not toxic for the study period of three weeks. Full article
(This article belongs to the Special Issue Advances in Melanoma Targeted Therapy)
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