Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Trends Pharmacol Sci. 2020 Oct;41(10):684-686. doi: 10.1016/j.tips.2020.08.008. Epub 2020 Sep 4.
In a recent study, Saraswat and colleagues identified a novel proteolysis targeting chimera (PROTAC), ARV-825 (ARV), that efficiently degrades bromodomain-containing protein 4 (BRD4) to drug the 'undruggable' MYC in pancreatic cancer. ARV-loaded polyethylene glycol-poly lactic acid-co-glycolic acid (PLGA-PEG) polymeric nanoparticles (ARV-NPs) showed promising anticancer activity in both 2D cell culture and 3D multicellular tumor spheroid models of pancreatic cancer. This study demonstrates a unique therapeutic strategy in which targeting BRD4 for degradation via the E3 ubiquitin ligase cereblon (CRBN) pathway leads to sustained inhibition of oncogenic MYC expression for effective treatment of pancreatic cancer.
在最近的一项研究中，Saraswat 和他的同事们发现了一种新型的蛋白水解靶向嵌合体（PROTAC），即 ARV-825（ARV），它能够有效地降解含溴结构域蛋白 4（BRD4），从而抑制胰腺癌中“不可成药”的 MYC。负载 ARV 的聚乙二醇-聚乳酸-co-羟基乙酸（PLGA-PEG）聚合物纳米粒（ARV-NPs）在二维细胞培养和胰腺癌三维多细胞肿瘤球体模型中均显示出有前景的抗癌活性。这项研究展示了一种独特的治疗策略，通过 E3 泛素连接酶 cereblon（CRBN）途径靶向 BRD4 进行降解，导致持续抑制致癌 MYC 表达，从而有效治疗胰腺癌。
