Merkel Cell Polyomavirus-Pathophysiology and Treatment in the Era of Gene-Targeted Therapies.

IF 9 2区 医学 Q1 VIROLOGY Reviews in Medical Virology Pub Date : 2024-09-01 DOI:10.1002/rmv.2580
Trairong Chokwassanasakulkit, Nigel A J McMillan
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Abstract

Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects.

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梅克尔细胞多瘤病毒--基因靶向疗法时代的病理生理学与治疗。
梅克尔细胞多瘤病毒(MCPyV)是诱发梅克尔细胞癌(MCC)的重要因素,MCC是一种侵袭性皮肤癌,复发率高,存活率低。事实上,它是最致命的皮肤癌。MCPyV 阳性 MCC 的确切传播途径尚不清楚,但有几个因素可能会诱发其发展。MCC的常规治疗效果不佳,尤其是对转移患者,因此显然需要新的治疗方案。基因靶向疗法在治疗 MCC 方面大有可为,包括使用 siRNA 和 CRISPR/Cas (C/Cas),但重要的是,这些疗法都尚未进入临床试验阶段。一些 siRNA 产品已经获得了美国食品及药物管理局(FDA)的许可,而 C/Cas 也已进入临床试验阶段,尽管它们是用于治疗 MCC 以外的疾病。从临床前研究走向临床必须克服许多挑战。在这篇综述中,我们全面总结了目前对 MCC 的认识,尤其关注 MCPyV 阳性 MCC 以及基因靶向疗法的现状。此外,我们还讨论了阻碍 MCC 研究的主要障碍,并探讨了未来前景。
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来源期刊
Reviews in Medical Virology
Reviews in Medical Virology 医学-病毒学
CiteScore
21.40
自引率
0.90%
发文量
88
期刊介绍: Reviews in Medical Virology aims to provide articles reviewing conceptual or technological advances in diverse areas of virology. The journal covers topics such as molecular biology, cell biology, replication, pathogenesis, immunology, immunization, epidemiology, diagnosis, treatment of viruses of medical importance, and COVID-19 research. The journal has an Impact Factor of 6.989 for the year 2020. The readership of the journal includes clinicians, virologists, medical microbiologists, molecular biologists, infectious disease specialists, and immunologists. Reviews in Medical Virology is indexed and abstracted in databases such as CABI, Abstracts in Anthropology, ProQuest, Embase, MEDLINE/PubMed, ProQuest Central K-494, SCOPUS, and Web of Science et,al.
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