Institute of Biomedicine and Glycomics and School and Pharmacy and Medical Sciences, Griffith University, Gold Coast, Australia.
Rev Med Virol. 2024 Sep;34(5):e2580. doi: 10.1002/rmv.2580.
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.
Merkel 细胞多瘤病毒（MCPyV）是 Merkel 细胞癌（MCC）发展的重要因素，MCC 是一种侵袭性皮肤癌，具有高复发率和低生存率。事实上，它是最致命的皮肤癌。MCPyV 阳性 MCC 的确切传播途径仍不清楚，但有几个因素可能触发其发展。MCC 的常规治疗方法效果并不高，特别是对于转移性患者，因此迫切需要新的治疗选择。基因靶向治疗为 MCC 治疗带来了巨大的希望，包括使用 siRNA 和 CRISPR/Cas（C/Cas），但至关重要的是，这些方法尚未转化为临床试验。有几个 siRNA 产品已获得 FDA 许可，而 C/Cas 已进入临床试验，尽管是用于 MCC 以外的病症，这一事实验证了这种方法的有效性。要将基础研究转化为临床应用，还需要克服许多挑战。在这篇综述中，我们全面总结了目前对 MCC 的认识，特别关注 MCPyV 阳性 MCC 和基因靶向治疗的现状。此外，我们还讨论了阻碍 MCC 研究的主要障碍，并探讨了未来的前景。
