Article
Medicine, General & Internal
Danielle Brazel, Priyanka Kumar, Hung Doan, Tianyu Pan, Weining Shen, Ling Gao, Justin T. Moyers
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with increasing incidence. This study aimed to identify actionable alterations associated with tumor mutation burden (TMB) using the OncoKB database. The findings suggest that targeted therapies may be a viable treatment option for selected MCC patients.
Review
Biochemistry & Molecular Biology
Elena Dellambra, Maria Luigia Carbone, Francesca Ricci, Francesco Ricci, Francesca Romana Di Pietro, Gaia Moretta, Sofia Verkoskaia, Elisa Feudi, Cristina M. Failla, Damiano Abeni, Luca Fania
Summary: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. Treatment of advanced MCC tumors with immune checkpoint inhibitors has shown effective results, highlighting the importance of immunotherapy in managing this disease.
Article
Virology
Chiara Mazziotta, Christian Felice Cervellera, Giada Badiale, Ilaria Vitali, Antoine Touze, Mauro Tognon, Fernanda Martini, John Charles Rotondo
Summary: MCCP and MCCN cells can be distinguished from each other based on their retinoic gene signature, and MCCP has several upregulated genes related to the nervous system and Merkel cell development. The study suggests a neuroendocrine origin for MCCP, which could potentially lead to the development of retinoid-based therapies for MCC.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Oncology
Steffi Silling, Alexander Kreuter, Thilo Gambichler, Thomas Meyer, Eggert Stockfleth, Ulrike Wieland
Summary: Merkel cell polyomavirus (MCPyV) is a common virus on human skin, leading to the development of a rare but aggressive Merkel cell carcinoma (MCC) in older individuals, especially those with fair skin, male sex, and immunosuppression. The incidence of MCC, caused by MCPyV or UV damage, is increasing globally, with risk factors including male sex, older age, fair skin, intense UV exposure, and immunosuppression. Early diagnosis and prompt treatment are crucial for reducing MCC morbidity and mortality.
Article
Medicine, Research & Experimental
Monique E. Verhaegen, Paul W. Harms, Julia J. Van Goor, Jacob Arche, Matthew T. Patrick, Dawn Wilbert, Haley Zabawa, Marina Grachtchouk, Chia-Jen Liu, Kevin Hu, Michael C. Kelly, Ping Chen, Thomas L. Saunders, Stephan Weidinger, Li-Jyun Syu, John S. Runge, Johann E. Gudjonsson, Sunny Y. Wong, Isaac Brownell, Marcin Cieslik, Aaron M. Udager, Arul M. Chinnaiyan, Lam C. Tsoi, Andrzej A. Dlugosz
Summary: Merkel cell carcinoma (MCC) is an aggressive skin cancer that expresses specific genes similar to skin-resident Merkel cells. Researchers have used ATOH1 to induce MCC development in mice by cellular reprogramming. By conditionally expressing MCPyV TAgs and ATOH1 in mouse epidermal cells, they were able to generate MCC-like tumor cells from hair follicles. The study confirmed the similarity between mouse and human MCCs and revealed that loss of p53 is necessary for the progression of MCC in this mouse model.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Oncology
Roland Houben, Bueke Celikdemir, Thibault Kervarrec, David Schrama
Summary: By studying the cancer-inducing ability of polyomaviruses, researchers have made significant progress in understanding tumor suppressor proteins and have identified Merkel cell polyomavirus (MCPyV) as a human polyomavirus-induced cancer. Intensive research has since uncovered many details about the virus-host interaction and the molecular mechanisms by which MCPyV causes cancer. This review summarizes the current knowledge on MCPyV and MCC and discusses remaining questions.
Review
Microbiology
Nathan A. Krump, Jianxin You
Summary: MCPyV infection is common in the skin and can lead to MCC, with potential for prophylactic and targeted intervention. Understanding host responses to control MCPyV infection could inform preventive measures, while vulnerabilities in MCC associated with MCPyV could provide insights for potential solutions. The study proposes a model where inadequate restriction of MCPyV infection in aging and chronically UV-damaged skin may contribute to MCC tumorigenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Thibault Kervarrec, Silke Appenzeller, Anne Tallet, Marie-Laure Jullie, Pierre Sohier, Francois Guillonneau, Arno Rutten, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Beneton, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Sebastien Visee, Michael Herfs, Antoine Touze, Serge Guyetant, Mahtab Samimi, Roland Houben, David Schrama
Summary: This study found that wildtype MCPyV genomes and VP1 transcription exist in a subset of MCC.
Review
Biochemistry & Molecular Biology
Karolina Stachyra, Monika Dudzisz-Sledz, Elzbieta Bylina, Anna Szumera-Cieckiewicz, Mateusz J. Spalek, Ewa Bartnik, Piotr Rutkowski, Anna M. Czarnecka
Summary: Merkel cell carcinoma is a rare and highly aggressive skin cancer that develops in sun-exposed areas. It can be categorized into viral positive and viral negative types, with the latter having a high mutation burden and abnormal gene expression. Surgical excision is the main treatment for MCC, while radiotherapy is effective but can lead to chemoresistance. Immunotherapy has become the standard first-line therapy for advanced MCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
John Charles Rotondo, Chiara Mazziotta, Carmen Lanzillotti, Mauro Tognon, Fernanda Martini
Summary: This review discusses the impact of epigenetic mechanisms on Merkel cell polyomavirus (MCPyV)-driven Merkel Cell Carcinoma (MCC), highlighting the importance of histone posttranslational modifications, DNA methylation, and microRNA regulation. The dysregulation of these epigenetic processes may have clinical significance for MCC diagnosis, prognosis, and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Luz E. Ortiz, Alexander M. Pham, Hyun Jin Kwun
Summary: MCPyV's LT antigen interacts with E3 ligases to limit viral replication, and Lys 585 residue in LT is identified as the ubiquitin conjugation site, impacting MCPyV genome replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
James A. DeCaprio
Summary: Merkel cell carcinoma (MCC) has two distinct etiologies, with one caused by viral DNA integration and the other by UV damage. Despite different causes, both forms of MCC have similar presentation, prognosis, and response to therapy. Oncogenic transcriptional programs, cell proliferation rates, and neuroendocrine differentiation programs play important roles in both types of MCC.
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 16, 2021
(2021)
Article
Medicine, General & Internal
Attila Mokanszki, Gabor Mehes, Szilvia Lilla Csoma, Sandor Kollar, Yi-Che Chang Chien
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy often associated with sun exposure, with Merkel cell polyomavirus (MCPyV) implicated in its pathogenesis. Genetic differences were identified between MCPyV-positive and -negative MCC cases, with more pathogenic variants found in virus-associated cases. Further research is needed to understand the clinical implications of these findings.
Article
Oncology
Thilo Gambichler, Britta Majchrzak-Stiller, Ilka Peters, Juergen C. Becker, Johanna Strotmann, Nessr Abu Rached, Thomas Muller, Waldemar Uhl, Marie Buchholz, Chris Braumann
Summary: The study demonstrates that GP-2250 has anti-neoplastic effects on MCPyV-negative tumor cells by inhibiting viability, proliferation, and migration, and downregulating protein expression of aberrant tumorigenic pathways.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Virology
Emily J. Koubek, Jillian S. Weissenrieder, Luz E. Ortiz, Nnenna Nwogu, Alexander M. Pham, J. Dylan Weissenkampen, Jessie L. Reed, Jeffrey D. Neighbors, Raymond J. Hohl, Hyun Jin Kwun
Summary: Merkel cell carcinoma (MCC) is an aggressive form of skin cancer caused by the Merkel cell polyomavirus (MCPyV). A recent study found that schweinfurthin compounds can selectively inhibit MCPyV-infected cancer cell lines and induce apoptosis. This discovery suggests a promising new therapeutic option for virus-induced MCC.
