Department of Pathology, University of Oklahoma Health Sciences Center, BMSB401A, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
Int J Mol Sci. 2024 Apr 2;25(7):3958. doi: 10.3390/ijms25073958.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with a low 5-year overall survival rate. It is the third-leading cause of cancer-related deaths in the United States. The lack of robust therapeutics, absence of effective biomarkers for early detection, and aggressive nature of the tumor contribute to the high mortality rate of PDAC. Notably, the outcomes of recent immunotherapy and targeted therapy against PDAC remain unsatisfactory, indicating the need for novel therapeutic strategies. One of the newly described molecular features of PDAC is the altered expression of protein arginine methyltransferases (PRMTs). PRMTs are a group of enzymes known to methylate arginine residues in both histone and non-histone proteins, thereby mediating cellular homeostasis in biological systems. Some of the PRMT enzymes are known to be overexpressed in PDAC that promotes tumor progression and chemo-resistance via regulating gene transcription, cellular metabolic processes, RNA metabolism, and epithelial mesenchymal transition (EMT). Small-molecule inhibitors of PRMTs are currently under clinical trials and can potentially become a new generation of anti-cancer drugs. This review aims to provide an overview of the current understanding of PRMTs in PDAC, focusing on their pathological roles and their potential as new therapeutic targets.
胰腺导管腺癌 (PDAC) 是一种致命的恶性疾病，其 5 年总生存率较低。它是美国癌症相关死亡的第三大原因。缺乏强大的治疗方法、缺乏有效的早期检测生物标志物以及肿瘤的侵袭性导致 PDAC 的死亡率居高不下。值得注意的是，最近针对 PDAC 的免疫疗法和靶向疗法的结果仍不尽如人意，表明需要新的治疗策略。PDAC 的新描述的分子特征之一是蛋白精氨酸甲基转移酶 (PRMTs) 的表达改变。PRMTs 是一组已知将精氨酸残基甲基化到组蛋白和非组蛋白蛋白中的酶，从而调节生物系统中的细胞内稳态。一些 PRMT 酶在 PDAC 中过表达，通过调节基因转录、细胞代谢过程、RNA 代谢和上皮间质转化 (EMT) 来促进肿瘤进展和化疗耐药性。PRMT 的小分子抑制剂目前正在临床试验中，有可能成为新一代抗癌药物。本综述旨在概述 PRMTs 在 PDAC 中的最新研究进展，重点介绍它们的病理作用及其作为新治疗靶点的潜力。
