ArticleAmerican journal of cancer research2021
Epigenetic heterogeneity promotes acquired resistance to BET bromodomain inhibition in ovarian cancer.
Article in American journal of cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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
7 citing papers in PubMed, 6 citations in OpenAlex.
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- The extra-terminal domain drives the role of BET proteins in transcription.Nucleic acids research · 2026Article
- Aurora kinases signaling in cancer: from molecular perception to targeted therapies.Molecular cancer · 2025Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Distinct layers of BRD4-PTEFb reveal bromodomain-independent function in transcriptional regulation.Molecular cell · 2023Article
- The role of distinct BRD4 isoforms and their contribution to high-grade serous ovarian carcinoma pathogenesis.Molecular cancer · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BET bromodomain inhibitors (BETi) are promising therapeutic regimens for epithelial ovarian cancer (EOC). However, early-stage clinical trials indicate that drug tolerance may limit their anti-tumor efficacy. Here, we show that JQ1-refractory EOC cells acquire reversible resistance to BET inhibition and remain dependent on BRD4 function. The insensitivity is driven by a unique non-genetic mechanism that involves clonal selection for a pre-existing cell subpopulation with ample acetylated histones and sufficient nuclear phase-separated BRD4 droplets to counteract BETi antagonism. A vertical combination approach by co-blocking BET proteins and downstream Aurora kinases proves to achieve more complete responses than single inhibitors. Collectively, our study implicates epigenetic heterogeneity in therapeutic resistance to chromatin-targeted agents and proposes a rational strategy to address this anticipated clinical dilemma.
Indexed as
Identifiers
34249442PMC8263684W3182238336What OpenQuestion holds
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.