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Adjuvant Therapy for Melanoma: Recent and Future Developments

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 14202

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Special Issue Editor

Dr. Satoshi Fukushima

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Guest Editor

Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
Interests: adjuvant therapy; melanoma; immunotherapy

Special Issue Information

Dear Colleagues,

Adjuvant therapy utilizing immune checkpoint blockades (anti-PD-1 Abs) and targeted therapies (BRAF/MEK inhibitors) against melanoma have been approved several years ago. Now these drugs are widely used in many countries. However, the real-world evidence of adjuvant therapy against melanoma is still lacking. For examples, response rates of the recurrent melanoma to the immune checkpoint blockades and targeted therapies are unknown. There is not enough evidence which therapies should be used firstly when the melanoma showed BRAF V600 mutation. Furthermore, neoadjuvant therapies are now tested its efficacy in many trials.

In this Special Issue: Adjuvant Therapy for Melanoma: Recent and Future Developments, the recent evidence of adjuvant therapy for melanoma will be reviewed. And new original research articles for the future developments of adjuvant therapy are going to be presented. Overall, we are confident that this Special Issue will be of interest to the broad readership of the journal. It will provide substantial information covering our current knowledge and future expectations on adjuvant therapy against melanoma.

Dr. Satoshi Fukushima
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. 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

Adjuvant Therapy
Melanoma
Immunotherapy
Targeted therapy
Neoadjuvant therapy

Published Papers (3 papers)

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Research

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13 pages, 1457 KiB

Open AccessArticle

Disease Recurrence during Adjuvant Immune Checkpoint Inhibitor Treatment in Metastatic Melanoma: Clinical, Laboratory, and Radiological Characteristics in Patients from a Single Tertiary Referral Center

by Jonas K. Kurzhals, Gina Klee, Victoria Hagelstein, Detlef Zillikens, Patrick Terheyden and Ewan A. Langan

Int. J. Mol. Sci. 2022, 23(18), 10723; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810723 - 14 Sep 2022

Cited by 3 | Viewed by 1480

Abstract

Despite the dramatic improvements in recurrence-free survival in patients with metastatic melanoma treated with immune checkpoint inhibitors (ICI), a number of patients develop metastases during adjuvant therapy. It is not currently possible to predict which patients are most likely to develop disease recurrence due to a lack of reliable biomarkers. Thus, we retrospectively analyzed the case records of all patients who commenced adjuvant ICI therapy between January 2018 and December 2021 in a single university skin cancer center (n = 46) (i) to determine the rates of disease recurrence, (ii) to examine the utility of established markers, and (iii) to examine whether re-challenge with immunotherapy resulted in clinical response. Twelve out of forty-six (26%) patients developed a relapse on adjuvant immunotherapy in our cohort, and the median time to relapse was 139 days. Adjuvant immunotherapy was continued in three patients. Of the twelve patients who developed recurrence during adjuvant immunotherapy, seven had further disease recurrence within the observation period, with a median time of 112 days after the first progress. There was no significant difference comparing early recurrence (<180 days after initiation) on adjuvant immunotherapy to late recurrence (>180 days after initiation) on adjuvant immunotherapy. Classical tumor markers, including serum lactate dehydrogenase (LDH) and S-100, were unreliable for the detection of disease recurrence. Baseline lymphocyte and eosinophil counts and those during immunotherapy were not associated with disease recurrence. Interestingly, patients with NRAS mutations were disproportionately represented (60%) in the patients who developed disease recurrence, suggesting that these patients should be closely monitored during adjuvant therapy. Full article

(This article belongs to the Special Issue Adjuvant Therapy for Melanoma: Recent and Future Developments)

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Review

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17 pages, 1363 KiB

Open AccessReview

The Role of Calcium Signaling in Melanoma

by Haoran Zhang, Zhe Chen, Aijun Zhang, Anisha A. Gupte and Dale J. Hamilton

Int. J. Mol. Sci. 2022, 23(3), 1010; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031010 - 18 Jan 2022

Cited by 15 | Viewed by 4274

Abstract

Calcium signaling plays important roles in physiological and pathological conditions, including cutaneous melanoma, the most lethal type of skin cancer. Intracellular calcium concentration ([Ca²⁺]i), cell membrane calcium channels, calcium related proteins (S100 family, E-cadherin, and calpain), and Wnt/Ca²⁺ pathways are related to melanogenesis and melanoma tumorigenesis and progression. Calcium signaling influences the melanoma microenvironment, including immune cells, extracellular matrix (ECM), the vascular network, and chemical and physical surroundings. Other ionic channels, such as sodium and potassium channels, are engaged in calcium-mediated pathways in melanoma. Calcium signaling serves as a promising pharmacological target in melanoma treatment, and its dysregulation might serve as a marker for melanoma prediction. We documented calcium-dependent endoplasmic reticulum (ER) stress and mitochondria dysfunction, by targeting calcium channels and influencing [Ca²⁺]i and calcium homeostasis, and attenuated drug resistance in melanoma management. Full article

(This article belongs to the Special Issue Adjuvant Therapy for Melanoma: Recent and Future Developments)

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16 pages, 1176 KiB

Open AccessReview

microRNAs in the Regulation of Melanogenesis

by Yekatsiaryna Hushcha, Irene Blo, Lucia Oton-Gonzalez, Giulia Di Mauro, Fernanda Martini, Mauro Tognon and Monica De Mattei

Int. J. Mol. Sci. 2021, 22(11), 6104; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116104 - 05 Jun 2021

Cited by 25 | Viewed by 7782

Abstract

Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs. This review collects data on the miRNAs involved in melanogenesis and how these miRNAs can modulate target gene expression. Bringing to light the biological function of miRNAs could lead to a wider understanding of epigenetic melanogenesis regulation and its dysregulation. This knowledge may constitute the basis for developing innovative treatment approaches for pigmentation dysregulation. Full article

(This article belongs to the Special Issue Adjuvant Therapy for Melanoma: Recent and Future Developments)

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