Melanoma: From Molecular Mechanisms to Therapeutic Opportunities—Series 2

Dear Colleagues,

We are pleased to announce the second edition of our Special Issue. The first edition attracted the interest of researchers around the world. The publications that are freely available for download are listed at the following:

Cells website: https://www.mdpi.com/journal/cells/special_issues/Melanoma_Molecular_Mechanism

Malignant melanoma remains a formidable challenge, with ~106,110 new cases and ~7,180 deaths in the United States in 2021. Drug and immune resistance, together with invasion and metastasis, determine tumor progression, and, ultimately, patient survival. With the highest mortality rate among skin cancers, cutaneous melanoma is associated with driver mutations in MAPK and other signaling pathways, including RAS/PI3K/AKT, p16INK4a/CDK4/RB, WNT, and p53. Activating mutations are primarily in the V600 or K601 of BRAF (50% of melanomas), Q61 of NRAS (>20%), and LOF mutations in NF1 (10%). Although combinations of targeted kinase inhibitors for BRAF and MEK, combined with immune checkpoint inhibitors, have improved progression-free and overall survival of melanoma patients, ~75% of melanomas recur after BRAF copy number gains, alternative splicing, MEK1/2, and NRAS gain-of-function mutations; 20% of BRAFi-resistant melanomas upregulate compensatory PI3K/AKT survival pathways. Although treatment for recalcitrant NRAS-mutant metastatic tumors has advanced, with immunotherapies anti–PD-1, anti-PD-L1, and/or anti-CTLA4 proving efficacious, many patients remain unresponsive, and chemotherapy with dacarbazine, temozolomide, or carboplatin shows limited success.  There is a compelling rationale to examine unexploited pathways. Resistance has been attributed to subpopulations of “melanoma initiating cells”, highly tumorigenic cancer stem cells characterized by melanosphere formation, and expression of specific cancer stem cell markers.

This Special Issue will publish original articles and reviews focusing on novel targets for therapeutic intervention; biomarkers for screening, predicting treatment response, and monitoring disease progression; and mechanistic insights and advances in molecular and cellular pathways involved in melanomagenesis and progression. Topics of interest include mechanisms underlying melanoma progression and treatment response, signal transduction, melanoma-initiating cells, drug resistance, invasiveness, immune evasion, and metastasis. There remains an urgent need to identify novel targets and develop new combinatorial therapeutic approaches that can overcome drug resistance mechanisms.

We look forward to receiving your contributions to this Special Issue.

Prof. Dr. Cynthia Simbulan-Rosenthal
Dr. Dean S. Rosenthal
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 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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells 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 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.