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.
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
Multidisciplinary Sciences
Jenni Jaatinen, Tuukka Veija, Marko Salmikangas, Tom Bohling, Harri Sihto, Virve Koljonen
Summary: MCC tumor samples frequently exhibit phosphorylated ALK, which correlates with MCPyV positivity, younger age, absence of metastases at diagnosis, and better MCC-specific survival. In contrast, only a small number of MCC cell lines show low ALK phosphorylation, suggesting a disparity in ALK activity between patient derived tumors and cell line samples. Additional studies using more advanced disease models such as xenografts are needed to determine if ALK is a viable treatment target in MCC.
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)
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
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)
Article
Oncology
Takeshi Iwasaki, Kazuhiko Hayashi, Michiko Matsushita, Daisuke Nonaka, Kenichi Kohashi, Satoshi Kuwamoto, Yoshihisa Umekita, Yoshinao Oda
Summary: In MCPyV-positive MCCs, higher activation of the JAK2 and MEK-ERK pathways was observed, while the JAK inhibitor ruxolitinib could inhibit MEK-ERK pathway activation. These findings suggest that the JAK-STAT and MEK-ERK signaling pathways may serve as potential targets for MCPyV-negative MCC treatment.
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
Dermatology
K. Maurus, C. Kosnopfel, H. Kneitz, S. Appenzeller, D. Schrama, V Glutsch, S. Roth, E. Gerhard-Hartmann, M. Rosenfeldt, L. Moehrmann, M. Froehlich, D. Huebschmann, A. Stenzinger, H. Glimm, S. Froehling, M. Goebeler, A. Rosenwald, H. Kutzner, B. Schilling
Summary: Genetic alterations in genes of the MAPK pathway were identified in cutaneous EH patients, suggesting a potential role in the formation of this benign tumor.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Oncology
Roland Houben, Sonja Hesbacher, Bhavishya Sarma, Carolin Schulte, Eva-Maria Sarosi, Sabine Popp, Christian Adam, Thibault Kervarrec, David Schrama
Summary: GSK3 inhibitors, such as CHIR99021, have been identified as potential therapeutics for Merkel cell carcinoma (MCC) by repressing TA expression in MCC cells, demonstrating in vivo antitumor activity in a MCC xenograft mouse model. This study provides a promising approach for future treatment of MCC by targeting virus-encoded T antigens.
Review
Oncology
Clara Esnault, David Schrama, Roland Houben, Serge Guyetant, Audrey Desgranges, Camille Martin, Patricia Berthon, Marie-Claude Viaud-Massuard, Antoine Touze, Thibault Kervarrec, Mahtab Samimi
Summary: Antibody-drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Tremendous progress has been observed in therapeutic approaches for advanced skin cancer patients. However, current targeted therapies or immune checkpoint-blocking antibodies outperform conventional chemotherapy, with proven benefit to survival. Nevertheless, these therapies still have limitations such as primary and acquired resistances as well as adverse events. Therefore, ADCs appear as an emerging therapeutic option in oncodermatology.
Letter
Dermatology
Simon Barbieux, Anne Tallet, Christine Collin, Matthias Tallegas, Flore Delalande, Guido Bens, Annie Levy, Athanasios Kalampokas, David Schrama, Roland Houben, Antoine Touze, Jeremy Garcia, Nicolas Macagno, Romain Appay, Mahtab Samimi, Serge Guyetant, Thibault Kervarrec
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
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.
Article
Oncology
Roland Houben, Pamela Alimova, Bhavishya Sarma, Sonja Hesbacher, Carolin Schulte, Eva-Maria Sarosi, Christian Adam, Thibault Kervarrec, David Schrama
Summary: The treatment of Merkel cell carcinoma, a deadly skin cancer caused by Merkel cell polyomavirus, is challenging. This study identified a compound, previously described as an inhibitor of Aurora kinase A, that represses the growth of Merkel cell carcinoma cells by inhibiting the expression of viral proteins. However, it was found that the effect is not related to the inhibition of Aurora kinase A, but possibly due to an unknown GSK3-inhibitory activity of the compound, which was demonstrated to have therapeutic potential in immunocompromised mice.
Article
Medicine, General & Internal
Roland Houben
Summary: A patient with chronic migraine and medication overuse headache experienced remarkable reduction in migraine symptoms after being infected with SARS-CoV-2. This suggests that SARS-CoV-2 infection may trigger mitigation of migraine.
JOURNAL OF MEDICAL CASE REPORTS
(2023)
Review
Biotechnology & Applied Microbiology
Bueke Celikdemir, Roland Houben, Thibault Kervarrec, Mahtab Samimi, David Schrama
Summary: Merkel cell carcinoma is a rare and highly aggressive form of skin cancer with unclear origin, but recent research has identified two distinct etiologic pathways. The significance of MCC research and the need for advancement in MCC treatment are highlighted due to its high mortality rate and limited therapeutic options.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Review
Cell Biology
Thibault Kervarrec, Daniel Pissaloux, Franck Tirode, Arnaud de la Fouchardiere, Pierre Sohier, Eric Frouin, Aymeric Hamard, Roland Houben, David Schrama, Anne Barlier, Bernard Cribier, Maxime Battistella, Nicolas Macagno
Summary: This article reviews the clinical, morphological, and molecular features of the benign sweat gland tumor poroma and its malignant counterpart porocarcinoma, and discusses the impact of their systematic molecular characterization on diagnosis, classification, prognosis, and therapeutic modalities.
Article
Biochemistry & Molecular Biology
Veronika Banicka, Marie Christine Martens, Rudiger Panzer, David Schrama, Steffen Emmert, Lars Boeckmann, Alexander Thiem
Summary: Defects in DNA repair pathways, such as nucleotide excision repair (NER) deficiency in Xeroderma pigmentosum (XP), have been found to be associated with a positive response to immune checkpoint inhibition (ICI) treatment. This study used CRISPR/Cas9 to disrupt XPA gene in melanoma cells and identified specific gene mutations that are related to DNA damage repair and cell survival. These findings provide a basis for further investigation on the immunological consequences of XPA disruption in melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
