Evidence map›Paper›PMID 40686478›Full record

ArticleNeuro-oncology2025

BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma.

Raghavendra Vadla, Brett Taylor, Yohei Miyake, Benjamin Lin, Daisuke Kawauchi, Shunichiro Miki, Nidhi Nathwani, Brandon M Jones, Yashpreet Kaur, Abhinaba Banerjee and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Raghavendra VadlaDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.ORCID 0000-0002-3903-2662
Brett TaylorMedical Scientist Training Program, University of California, San Diego, La Jolla, California, USA.
Yohei MiyakeDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Benjamin LinMedical Scientist Training Program, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Daisuke KawauchiDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Shunichiro MikiDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Nidhi NathwaniDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Brandon M JonesDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Yashpreet KaurDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Abhinaba BanerjeeDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Philip PhamDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Jonathan TsangDepartments of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Albert BaldwinUNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
David A NathansonDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Donald P PizzoDepartment of Pathology, University of California San Diego, La Jolla, California, USA.
C Ryan MillerDepartment of Pathology, Division of Neuropathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Frank B FurnariDivision of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.ORCID 0000-0003-1909-4361

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Predoctoral and Postdoctoral Training in Cancer Cell BiologyT32CA067754 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEAN Y.J. WANG · 1995 to 2026
$6.5M
Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5M
Credentialing next-generation human glioma models for precision therapeuticsR01CA258248 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Frank Furnari, Christopher Ryan Miller · 2022 to 2026
$3.0M
Therapeutic targeting mesenchymal transition in newly diagnosed and recurrent GBMR01NS134798 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Frank Furnari, Christopher Ryan Miller · 2024 to 2026
$1.9M
Genotypic Interactions in Brain Cancer HeterogeneityR56NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2023 to 2023
$537k
NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA258248NCI NIH HHS T32 CA067754NIH HHS R01CA258248NIH HHS R01NS080939NIH HHS R01NS134798NIH HHS R56NS080939NINDS NIH HHS R01 NS080939NINDS NIH HHS R01 NS134798NINDS NIH HHS R56 NS080939
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) displays remarkable cell state plasticity, a major contributor to therapeutic resistance and tumor progression. While epigenetic mechanisms play a central role in driving this plasticity, the key regulators remain poorly understood, and developing effective therapeutic strategies targeting them has been challenging.

methodsWe investigated the role of BRD2, a key regulator of NF-κB-mediated mesenchymal (MES) transition, using GBM patient-derived xenograft cell lines, CRISPR-mediated knock-in/knockout approaches, RNA-seq, and in vitro and in vivo modeling. BET inhibitors were employed to target MES gene expression and sensitize GBM to radiation therapy.

resultsWe found that PTEN loss induces RelA chromatin localization and acetylation-mediated recruitment of BRD2 to the MES gene promoters. BRD2 binding is essential for maintaining MES gene expression and phenotype. Genetic ablation or loss-of-function mutation of BRD2 bromodomains reverses MES transition, enhances radiation sensitivity, and improves survival in orthotopic xenograft models. Additionally, treatment with a brain-penetrant BD2-selective inhibitor suppresses the MES phenotype and increases radiation sensitivity of GBM stem cells in vitro.

conclusionOur study identifies BRD2 as a key mediator of MES transition in GBM, with its bromodomains playing a crucial role in driving cell state plasticity. Targeting BRD2 with BD2-selective inhibitors offers a promising therapeutic strategy to overcome radiation resistance and improve outcomes for GBM patients.

Indexed as

Brain NeoplasmsCell PlasticityGlioblastomaProtein Serine-Threonine KinasesAnimalsBromodomain Containing ProteinsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceRadiation ToleranceTranscription FactorsTumor Cells, CulturedXenograft Model Antitumor AssaysBRD2 protein, humanBromodomain Containing ProteinsProtein Serine-Threonine KinasesTranscription FactorsBET inhibitorsBRD2glioblastomamesenchymalNF-κB signaling

Identifiers

PMID40686478
PMCPMC12700489

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Registered trials

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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.