Kumar Devendra, Jain Stuti, Coulter Don W, Joshi Shantaram S, Chaturvedi Nagendra K
Department of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE 69198, USA.
Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE 69198, USA.
Cancers (Basel). 2023 Dec 15;15(24):5855. doi: 10.3390/cancers15245855.
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.
MYC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。最近，已表明蛋白质精氨酸甲基转移酶5（PRMT5）过表达与癌症中致癌性MYC功能相关，尤其是在胶质母细胞瘤和髓母细胞瘤等脑癌中。PRMT5调节包括MYC在内的癌基因，这些癌基因在髓母细胞瘤中常常失调。然而，PRMT5介导的翻译后修饰在这些癌蛋白稳定性中的作用仍知之甚少。PRMT5抑制对MYC的潜在影响使其成为各种癌症中一个有吸引力的靶点。PRMT5抑制剂是一类有前景的抗癌药物，已显示出临床前和初步临床疗效。在此，我们综述了使用小分子抑制剂靶向PRMT5的公开可用临床前和临床研究，并讨论了将其用于髓母细胞瘤治疗的前景。
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