Evidence map›Paper›PMID 41820523›Full record

ArticleNPJ precision oncology2026

BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.

Pingping Fang, Anais Saunders, Kay Minn, Katherine Jane Chua, Rebecca A Brooks, Danika Bakke, Gary S Leiserowitz, Neil Johnson, Shaomeng Wang, Jeremy Chien

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

10 authors.

Pingping FangDepartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Anais SaundersDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA.
Kay MinnNovogene, Sacramento, CA, USA.
Katherine Jane ChuaDepartment of Obstetrics and Gynecology, University of California Davis, Sacramento, CA, USA.
Rebecca A BrooksDepartment of Obstetrics and Gynecology, University of California Davis, Sacramento, CA, USA.
Danika BakkeCaris Life Sciences, Phoenix, AZ, USA.
Gary S LeiserowitzDepartment of Obstetrics and Gynecology, University of California Davis, Sacramento, CA, USA.
Neil JohnsonNuclear Dynamics and Cancer Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Shaomeng WangDepartment of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA.
Jeremy ChienDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA. jrchien@health.ucdavis.edu.

Funding

University of California Davis Pharmcology T32 Training Grant T32GM144303
6 · The paper itself

Abstract

Homologous recombination (HR) proficiency underlies intrinsic and acquired resistance to PARP inhibitors (PARPi). We identify a BRD4-dependent FOXM1-MYC transcriptional axis that sustains HR gene expression and limits PARPi response. ENCODE analyses revealed extensive co-occupancy of FOXM1 and MYC at regulatory regions of DNA repair genes, including BRCA1/2 and RAD51 paralogs, suggesting a shared HR program. Functionally, transient knockdown of FOXM1 or MYC reduced BRCA1/RAD51 transcripts, whereas sustained FOXM1 silencing triggered adaptive MYC upregulation that preserved HR output, indicating compensatory control. BET inhibition with (+)-JQ1 diminished FOXM1/MYC promoter occupancy at BRCA1 and RAD51, downregulated HR genes, and synergized with PARPi in viability and clonogenic assays. A BRD4 degrader (ZBC260) achieved potent BRD4 depletion at low nanomolar doses, suppressed FOXM1/MYC and HR gene expression, enhanced PARP1 trapping, and produced strong synergy with olaparib, including in patient-derived cancer cells. Clinically, BRD4 is highly expressed in ovarian cancer and independently predicts poor survival, outperforming FOXM1 and MYC. These data establish BRD4-directed disruption of the FOXM1-MYC axis as a strategy to induce "BRCAness" and broaden PARPi efficacy.

Identifiers

PMID41820523
PMCPMC13249861

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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.