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Special Issue "Melanoma Metastasis: New and Evolving Concepts"

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 7726

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Special Issue Editor

Prof. Ahmad Tarhini

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Guest Editor

Departments of Cutaneous Oncology & Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
Interests: melanoma; cutaneous oncology; immunooncology; immunotherapy; biomarkers

Special Issue Information

Dear Colleagues,

Deepening understanding of melanoma biology and host immunology has translated into major advances in managing melanoma in recent years. Molecularly targeted agents in the form of BRAF-MEK inhibitor combinations for BRAF mutant melanoma and immune checkpoint inhibitors targeting CTLA4, PD1, and LAG3 have drastically transformed clinical care. Despite these improvements, primary and acquired resistance remain a major barrier to successful treatment and, ultimately, long-term survival. Therefore, defining the underlying resistance mechanisms will be vital to improve the outcomes of the majority of patients, and understanding the biology behind clinical responses will be key to personalized treatment. In addition, determining the optimal treatment sequence for each patient may maximize the likelihood of clinical benefits. Enhancing our understanding of emerging technological advances combined with a growing knowledge of tumor biology and host immunology present major opportunities to better guide drug development in this disease.

This Special Issue will address evolving research topics related to neoadjuvant therapy of locoregionally advanced melanoma and first- and second-line treatment of metastatic melanoma. We will also address promising therapeutic agents under investigation in the anti-PD1 failure setting including adoptive cellular therapy and emerging mechanisms of immune resistance. Finally, we will review promising biomarkers of prognostic and therapeutic predictive value that may have applications in the clinic.

Prof. Ahmad Tarhini
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

melanoma
CTLA4
PD1
LAG3
BRAF
biomarkers
neoadjuvant
immune resistance
adoptive cellular therapy
uveal melanoma

Published Papers (4 papers)

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Research

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Open AccessArticle

Granulomatous and Sarcoid-like Immune-Related Adverse Events following CTLA4 and PD1 Blockade Adjuvant Therapy of Melanoma: A Combined Analysis of ECOG-ACRIN E1609 and SWOG S1404 Phase III Trials and a Literature Review

and

Cancers 2023, 15(9), 2561; https://doi.org/10.3390/cancers15092561 - 29 Apr 2023

Viewed by 1296

Abstract

Background: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. Methods: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. Results: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. Conclusions: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines. Full article

(This article belongs to the Special Issue Melanoma Metastasis: New and Evolving Concepts)

Open AccessArticle

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma

Danielle Vargas De Stefano

Cindy Sander

Arivarasan Karunamurthy

and

Cancers 2022, 14(20), 4973; https://doi.org/10.3390/cancers14204973 - 11 Oct 2022

Viewed by 1559

Abstract

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS. Full article

(This article belongs to the Special Issue Melanoma Metastasis: New and Evolving Concepts)

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Open AccessReview

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

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Cancers 2023, 15(6), 1884; https://doi.org/10.3390/cancers15061884 - 21 Mar 2023

Cited by 1 | Viewed by 2740

Abstract

Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5–15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3–6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4⁺ T-cells, myeloid-derived suppressor cells, and a low number of CD8⁺ T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood–CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors. This review summarizes the biology and anatomic features of melanoma LMD, as well as the current therapeutic approaches. Full article

(This article belongs to the Special Issue Melanoma Metastasis: New and Evolving Concepts)

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Open AccessReview

Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress

Danielle K. DePalo

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Jonathan S. Zager

Cancers 2023, 15(5), 1404; https://doi.org/10.3390/cancers15051404 - 23 Feb 2023

Viewed by 1505

Abstract

Locoregionally advanced and metastatic melanoma are complex diagnoses with a variety of available treatment options. Intralesional therapy for melanoma has been under investigation for decades; however, it has advanced precipitously in recent years. In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma. There has been significant progress since that time with other oncolytic viruses, toll-like receptor agonists, cytokines, xanthene dyes, and immune checkpoint inhibitors all under investigation as intralesional agents. Further to this, there has been exploration of numerous combinations of intralesional therapies and systemic therapies as various lines of therapy. Several of these combinations have been abandoned due to their lack of efficacy or safety concerns. This manuscript presents the various types of intralesional therapies that have reached phase 2 or later clinical trials in the past 5 years, including their mechanism of action, therapeutic combinations under investigation, and published results. The intention is to provide an overview of the progress that has been made, discuss ongoing trials worth following, and share our opinions on opportunities for further advancement. Full article

(This article belongs to the Special Issue Melanoma Metastasis: New and Evolving Concepts)

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Special Issue "Melanoma Metastasis: New and Evolving Concepts"

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