ArticleProceedings of the National Academy of Sciences of the United States of America2018
Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics.Infection · 2021Pooled it
- Harnessing MDM2-Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- Protease-mediated PRC1 dissociation promotes H2AK119ub remodeling during stress responses.The EMBO journal · 2026Article
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- Druggable target ATAD2 enhances the malignant progression and cooperates with E2F1 to up-regulate PDK1 expression in glioma.Genes & diseases · 2026Article
- BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.bioRxiv : the preprint server for biology · 2025Article
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- In-Cell Approach to Evaluate E3 Ligases for Use in Targeted Protein Degradation.Journal of the American Chemical Society · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A Review of the Bromodomain and Extraterminal Domain Epigenetic Reader Proteins: Function on Virus Infection and Cancer.Viruses · 2024Review
- Article
- MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma.BMC cancer · 2024Article
- Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide.Cell death & disease · 2024Article
- Targeted inhibition of BET proteins in HPV16-positive head and neck squamous cell carcinoma reveals heterogeneous transcriptional responses.Frontiers in oncology · 2024Article
- Trackplot: a fast and lightweight R script for epigenomic enrichment plots.Bioinformatics advances · 2024Article
- mRNA display reveals a class of high-affinity bromodomain-binding motifs that are not found in the human proteome.The Journal of biological chemistry · 2023Article
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
- Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1.Nature communications · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Competitive BET bromodomain inhibitors (BBIs) targeting BET proteins (BRD2, BRD3, BRD4, and BRDT) show promising preclinical activities against brain cancers. However, the BET protein-dependent glioblastoma (GBM)-promoting transcriptional network remains elusive. Here, with mechanistic exploration of a next-generation chemical degrader of BET proteins (dBET6), we reveal a profound and consistent impact of BET proteins on E2F1- dependent transcriptional program in both differentiated GBM cells and brain tumor-initiating cells. dBET6 treatment drastically reduces BET protein genomic occupancy, RNA-Pol2 activity, and permissive chromatin marks. Subsequently, dBET6 represses the proliferation, self-renewal, and tumorigenic ability of GBM cells. Moreover, dBET6-induced degradation of BET proteins exerts superior antiproliferation effects compared to conventional BBIs and overcomes both intrinsic and acquired resistance to BBIs in GBM cells. Our study reveals crucial functions of BET proteins and provides the rationale and therapeutic merits of targeted degradation of BET proteins in GBM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.