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Cancers
Special Issues
Merkel Cell Carcinoma: Clinical Challenges and New Developments
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Merkel Cell Carcinoma: Clinical Challenges and New Developments

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 2609

Special Issue Editor

Dr. Ling Gao

E-Mail Website
Guest Editor
Long Beach VA and Department of Dermatology, University of California, Irvine, CA, USA
Interests: Merkel cell carcinoma; immuno-oncology; tumor microenvironment; MCC mouse models; novel therapy and biomarkers

Special Issue Information

Dear Colleagues,

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer and its incidence has quadrupled in the past 20 years. Despite the recent approval of immune checkpoint inhibitors (ICI), their effective clinical use is encumbered by a high rate of resistance; moreover, clinical trials targeting genetic mutations and ICI resistance have not been successful. Currently there is no effective therapy for about 50% of MCC patients who are not candidates for ICIs and who have primary and acquired resistance to them. Since its discovery in 2008, MCC tumor heterogeneity has been attributed to variant disease etiologies, mediated by UV exposure or Merkel cell polyomavirus (MCPyV). Compared to MCPyV-positive MCCs, tumors without detectable MCPyV harbor a high tumor mutation burden with ultraviolet signatures. However, over the years, it has become clear that these two groups are largely similar in their clinical presentation, prognosis, and treatment response to ICIs. Thus, there is an urgent need to better understand heterogeneous MCC biology and uncover novel approaches that complement and extend current therapy.

Dr. Ling Gao
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

  • Merkel cell carcinoma
  • immuno-oncology
  • resistance mechanisms
  • novel therapies
  • Merkel cell polyomavirus
  • biomarkers
  • vaccine

Published Papers (2 papers)

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Review

11 pages, 268 KiB  
Review
Adjuvant Radiation in Resectable Node-Positive Merkel Cell Carcinoma in the Immunotherapy Era: Implications for Future and Ongoing Trials
by Paul Riviere, Anna M. Dornisch, Parag Sanghvi and Loren K. Mell
Cancers 2023, 15(23), 5550; https://doi.org/10.3390/cancers15235550 - 23 Nov 2023
Viewed by 820
Abstract
Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and [...] Read more.
Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: Clinical Challenges and New Developments)
19 pages, 1025 KiB  
Review
An Updated Review of the Biomarkers of Response to Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: Merkel Cell Carcinoma and Immunotherapy
by Adnan Fojnica, Kenana Ljuca, Saghir Akhtar, Zoran Gatalica and Semir Vranic
Cancers 2023, 15(20), 5084; https://doi.org/10.3390/cancers15205084 - 20 Oct 2023
Cited by 3 | Viewed by 1453
Abstract
Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least [...] Read more.
Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least one of the predictive biomarkers (PD-L1, high tumor mutational burden/TMB-H/, and microsatellite instability), their clinical significance in MCC is not fully understood. PD-L1 expression has been variably described in MCC, but its predictive value has not been established yet. Our literature survey indicates conflicting results regarding the predictive value of TMB in ICI therapy for MCC. Avelumab therapy has shown promising results in Merkel cell polyomavirus (MCPyV)-negative MCC patients with TMB-H, while pembrolizumab therapy has shown better response in patients with low TMB. A study evaluating neoadjuvant nivolumab therapy found no significant difference in treatment response between the tumor etiologies and TMB levels. In addition to ICI therapy, other treatments that induce apoptosis, such as milademetan, have demonstrated positive responses in MCPyV-positive MCC, with few somatic mutations and wild-type TP53. This review summarizes current knowledge and discusses emerging and potentially predictive biomarkers for MCC therapy with ICI. Full article
(This article belongs to the Special Issue Merkel Cell Carcinoma: Clinical Challenges and New Developments)
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