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BRD4：胶质瘤中一个新兴的潜在治疗靶点。

BRD4: An emerging prospective therapeutic target in glioma.

作者信息

Yang Hua, Wei Li, Xun Yang, Yang Anping, You Hua

机构信息

Department of Basic Medicine and Biomedical Engineering, School of Medicine, Foshan University, Foshan 528000, Guangdong Province, China.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong Province, China.

出版信息

Mol Ther Oncolytics. 2021 Mar 5;21:1-14. doi: 10.1016/j.omto.2021.03.005. eCollection 2021 Jun 25.

DOI:10.1016/j.omto.2021.03.005
PMID:33851008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8010576/
Abstract

Despite advances in treatment, the prognosis for glioma patients remains poor. Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extraterminal (BET) protein family, plays an important role in controlling oncogene expression and genome stability. In recent years, numerous BRD4 inhibitors have entered clinical trials and achieved exciting results in tumor treatment. Recent clinical studies have shown that BRD4 expression in glioma is significantly higher than in the adjacent normal brain tissue. BRD4 inhibitors effectively penetrate the blood-brain barrier and target glioma tumor tissues but have little effect on normal brain tissues. Thus, BRD4 is a target for the treatment of glioma. In this study, we discuss the progress in the use of BRD4 inhibitors for glioma treatment, their mechanism of action, and their broad potential clinical application.

摘要

尽管治疗方面取得了进展，但胶质瘤患者的预后仍然很差。含溴结构域蛋白4（BRD4）是溴结构域和额外末端（BET）蛋白家族的成员，在控制癌基因表达和基因组稳定性方面发挥着重要作用。近年来，众多BRD4抑制剂已进入临床试验，并在肿瘤治疗中取得了令人振奋的成果。最近的临床研究表明，胶质瘤中BRD4的表达明显高于相邻的正常脑组织。BRD4抑制剂能有效穿透血脑屏障并靶向胶质瘤肿瘤组织，但对正常脑组织影响很小。因此，BRD4是治疗胶质瘤的一个靶点。在本研究中，我们讨论了使用BRD4抑制剂治疗胶质瘤的进展、其作用机制以及广泛的潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/d4541c82b5ae/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/063b34cd1f80/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/81444d05aae8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/5a2defef9402/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/2547acf7e056/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/d4541c82b5ae/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/063b34cd1f80/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/81444d05aae8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/5a2defef9402/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/2547acf7e056/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186d/8010576/d4541c82b5ae/gr4.jpg

相似文献

[1]
BRD4: An emerging prospective therapeutic target in glioma.

Mol Ther Oncolytics. 2021-3-5

[2]
BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region.

Clin Transl Med. 2020-10

[3]
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Mol Cancer. 2018-11-22

[4]
A patent review of BRD4 inhibitors (2013-2019).

Expert Opin Ther Pat. 2019-12-13

[5]
Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells.

Int J Oncol. 2018-5

[6]
[Research Advances in the Mechanisms of BRD4 and Its Inhibitors in Hematologic Malignancies--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021-8

[7]
BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma.

Int J Immunopathol Pharmacol. 2015-3

[8]
Post-Translational Modifications of BRD4: Therapeutic Targets for Tumor.

Front Oncol. 2022-3-21

[9]
The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation.

Proc Natl Acad Sci U S A. 2015-7-7

[10]
Bromodomain inhibitor jq1 induces cell cycle arrest and apoptosis of glioma stem cells through the VEGF/PI3K/AKT signaling pathway.

Int J Oncol. 2019-8-29

引用本文的文献

[1]
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Epigenomes. 2025-7-28

[2]
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Cytotechnology. 2025-4

[3]
2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.

J Hepatocell Carcinoma. 2024-11-9

[4]
Novel BRD4-p53 Inhibitor SDU-071 Suppresses Proliferation and Migration of MDA-MB-231 Triple-Negative Breast Cancer Cells.

ACS Pharmacol Transl Sci. 2024-3-12

[5]
Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.

Int J Mol Sci. 2023-3-16

[6]
Discovery of novel BRD4-BD2 inhibitors via in silico approaches: QSAR techniques, molecular docking, and molecular dynamics simulations.

Mol Divers. 2024-4

[7]
Comprehensive analysis of the prognosis and immune infiltrates for the BET protein family reveals the significance of BRD4 in glioblastoma multiforme.

Front Cell Dev Biol. 2023-1-12

[8]
Facioscapulohumeral muscular dystrophy: the road to targeted therapies.

Nat Rev Neurol. 2023-2

[9]
Regulation of programmed cell death by Brd4.

Cell Death Dis. 2022-12-20

[10]
Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Neuro Oncol. 2023-6-2

本文引用的文献

[1]
Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts.

Oncogenesis. 2020-11-9

[2]
BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region.

Clin Transl Med. 2020-10

[3]
A Combination of BRD4 and HDAC3 Inhibitors Synergistically Suppresses Glioma Stem Cell Growth by Blocking GLI1/IL6/STAT3 Signaling Axis.

Mol Cancer Ther. 2020-12

[4]
BET bromodomains as novel epigenetic targets for brain health and disease.

Neuropharmacology. 2020-12-15

[5]
Inhibitors of bromodomain and extra-terminal proteins for treating multiple human diseases.

Med Res Rev. 2021-1

[6]
Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells.

Cell Death Dis. 2020-8-21

[7]
BRD4 prevents the accumulation of R-loops and protects against transcription-replication collision events and DNA damage.

Nat Commun. 2020-8-14

[8]
BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant prostate cancer.

Prostate Cancer Prostatic Dis. 2021-3

[9]
Brd4 inhibition ameliorates Pyocyanin-mediated macrophage dysfunction via transcriptional repression of reactive oxygen and nitrogen free radical pathways.

Cell Death Dis. 2020-6-15

[10]
Novel strategies targeting bromodomain-containing protein 4 (BRD4) for cancer drug discovery.

Eur J Med Chem. 2020-8-15

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