PDF(Pubmed)
Abstract：
Protein arginine methyltransferase 5 (PRMT5) inhibitors are a new class of antineoplastic agents showing promising preliminary clinical efficacy. Targeting an enzyme involved in a wide array of cellular and transcriptional pro-oncogenic processes, this class offers multifaceted tumor-suppressive effects. Partial response has been seen in adenoid cystic carcinoma from both GSK3326595 and JNJ-64619178, with four cases of stable disease seen with PRT543. Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811. Both alone and in combination with existing chemotherapies and immunotherapies, this class shows promising preliminary data, particularly in cancers with splicing mutations and DNA damage repair deficiencies. Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.
摘要：
蛋白质精氨酸甲基转移酶5（PRMT5）抑制剂是一类新型的抗肿瘤药物，具有良好的临床疗效。靶向参与广泛的细胞和转录前致癌过程的酶，这个类提供了多方面的肿瘤抑制作用。在GSK3326595和JNJ-64619178的腺样囊性癌中都看到了部分反应，在PRT543中发现了4例稳定的疾病。在PRT811的异柠檬酸脱氢酶1突变的多形性胶质母细胞瘤中，持久的完全反应非常重要。无论是单独还是与现有的化学疗法和免疫疗法相结合，这个类显示了有希望的初步数据，特别是在具有剪接突变和DNA损伤修复缺陷的癌症中。需要进一步的研究,还有临床试验，其数据将说明PRMT5抑制剂在血液系统和实体恶性肿瘤中的疗效。这项研究的目的是汇编PRMT5抑制剂在肿瘤学临床试验中的可用结果。
