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      Merkel Cell Carcinoma

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          Abstract

          Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

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          Clonal integration of a polyomavirus in human Merkel cell carcinoma.

          Huichen Feng, Masahiro Shuda, Yuan. Chang … (2008)
          Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence analysis of the 5387-base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.
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            Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.

            W. Lin, Masashi Narita, Scott Lowe … (2003)
            Cellular senescence is an extremely stable form of cell cycle arrest that limits the proliferation of damaged cells and may act as a natural barrier to cancer progression. In this study, we describe a distinct heterochromatic structure that accumulates in senescent human fibroblasts, which we designated senescence-associated heterochromatic foci (SAHF). SAHF formation coincides with the recruitment of heterochromatin proteins and the retinoblastoma (Rb) tumor suppressor to E2F-responsive promoters and is associated with the stable repression of E2F target genes. Notably, both SAHF formation and the silencing of E2F target genes depend on the integrity of the Rb pathway and do not occur in reversibly arrested cells. These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor.
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              PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.

              Paul T Nghiem, Shailender Bhatia, Evan J Lipson … (2016)
              Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.
              Article 0 comments Cited 233 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Shaker A. Mousa: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Biomedicines
                Journal ID (iso-abbrev): Biomedicines
                Journal ID (publisher-id): biomedicines
                Title: Biomedicines
                Publisher: MDPI
                ISSN (Electronic): 2227-9059
                Publication date (Electronic): 23 June 2021
                Publication date Collection: July 2021
                Volume: 9
                Issue: 7
                Electronic Location Identifier: 718
                Affiliations
                [1 ]Molecular and Cell Biology Laboratory, IDI-IRCCS, 00167 Rome, Italy; e.dellambra@ 123456idi.it
                [2 ]Experimental Immunology Laboratory, IDI-IRCCS, 00167 Rome, Italy; e.feudi@ 123456idi.it (E.F.); c.failla@ 123456idi.it (C.M.F.)
                [3 ]Histopathology Unit, IDI-IRCCS, 00167 Rome, Italy; francesca.ricci@ 123456idi.it
                [4 ]Dermatology Department, IDI-IRCCS, 00167 Rome, Italy; f.ricci@ 123456idi.it (F.R.); g.moretta@ 123456idi.it (G.M.); l.fania@ 123456idi.it (L.F.)
                [5 ]Oncology Department, IDI-IRCCS, 00167 Rome, Italy; f.dipietro@ 123456idi.it (F.R.D.P.); s.verkoskaia@ 123456idi.it (S.V.)
                [6 ]Clinical Epidemiology Unit, IDI-IRCCS, 00167 Rome, Italy; d.abeni@ 123456idi.it
                Author notes
                [* ]Correspondence: marialuigia.carbone@ 123456idi.it ; Tel.: +0039-0666464775
                Author information
                https://orcid.org/0000-0002-4329-3312
                https://orcid.org/0000-0002-3350-1210
                https://orcid.org/0000-0001-5991-8914
                https://orcid.org/0000-0002-0167-7617
                Article
                Publisher ID: biomedicines-09-00718
                DOI: 10.3390/biomedicines9070718
                PMC ID: 8301416
                PubMed ID: 34201709
                SO-VID: 67062fa1-250c-4bc0-a33f-2124140eecf0
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 17 May 2021
                Date accepted : 21 June 2021
                Categories
                Subject: Review

                Keywords: merkel cell carcinoma,merkel cell polyomavirus,immune checkpoint inhibitors
                Data availability:
                Keywords: merkel cell carcinoma, merkel cell polyomavirus, immune checkpoint inhibitors

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