BET家族蛋白包括BRD2、BRD3和BRD4，是乙酰化组蛋白标记的表观遗传读器，在多种人类恶性肿瘤的肿瘤发生和生长中扮演着多种角色，包括胶质母细胞瘤（GBM）。越来越多的研究已经证明BET蛋白是癌症治疗的有价值靶点。最近，已经报道了几种BRD4抑制剂和降解剂成功抑制了GBM的临床前和临床研究。然而，BRD4在GBM发病机制中的确切角色和机制尚未完全阐明或总结。本文重点总结了BRD4在GBM启动和发展过程中的角色和机制。此外，几种BRD4抑制剂已经评估为单一治疗方法或与化疗、放疗和免疫疗法联合使用的治疗目的。在此，我们批判性评估了评估各种BRD4抑制剂和降解剂作为治疗GBM的新治疗策略的研究。版权所有 © 2023 Elsevier Ltd.

The BET family proteins, comprising BRD2, BRD3 and BRD4, represent epigenetic readers of acetylated histone marks that play pleiotropic roles in the tumorigenesis and growth of multiple human malignancies, including glioblastoma (GBM). A growing body of investigation has proven BET proteins as valuable therapeutic targets for cancer treatment. Recently, several BRD4 inhibitors and degraders have been reported to successfully suppress GBM in preclinical and clinical studies. However, the precise role and mechanism of BRD4 in the pathogenesis of GBM have not been fully elucidated or summarized. This review focuses on summarizing the roles and mechanisms of BRD4 in the context of the initiation and development of GBM. In addition, several BRD4 inhibitors have been evaluated for therapeutic purposes as monotherapy or in combination with chemotherapy, radiotherapy, and immune therapies. Here, we provide a critical appraisal of studies evaluating various BRD4 inhibitors and degraders as novel treatment strategies against GBM.Copyright © 2023. Published by Elsevier Ltd.