文章：

PRMT5作为MYC扩增型髓母细胞瘤的潜在治疗靶点

PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma

原文发布日期：15 December 2023

DOI: 10.3390/cancers15245855

类型: Article

开放获取: 是

英文摘要：

MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Recently, protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. Here, we review the publicly available preclinical and clinical studies on PRMT5 targeting using small molecule inhibitors and discuss the prospects of using them in medulloblastoma therapy.

摘要翻译： 

MYC基因扩增或过表达在3组髓母细胞瘤中最为常见，且与不良临床预后呈正相关。近期研究表明，蛋白质精氨酸甲基转移酶5（PRMT5）的过表达与MYC在癌症中的致瘤功能相关，特别是在胶质母细胞瘤和髓母细胞瘤等脑部肿瘤中。PRMT5能够调控包括MYC在内的多种癌基因，这些基因在髓母细胞瘤中常出现异常表达。然而，PRMT5介导的翻译后修饰对这些癌蛋白稳定性的调控机制尚不明确。PRMT5抑制对MYC的潜在影响使其成为多种癌症中极具吸引力的治疗靶点。PRMT5抑制剂作为一类前景广阔的抗癌药物，已在临床前及初步临床研究中展现出疗效。本文系统综述了目前公开的关于小分子抑制剂靶向PRMT5的临床前及临床研究，并探讨了其在髓母细胞瘤治疗中的应用前景。

原文链接：

PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma