ArticleNature communications2021
Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Radiotherapy Response Patterns in Thoracic NUT Carcinoma: A Case Report.Respirology case reports · 2026Article
- EP300 deficiency leads to chronic replication stress mediated by defective replication fork protection.Nature communications · 2025Article
- BRD4 inhibition sensitizes glioblastoma to radiotherapy by suppressing super-enhancer-driven COL1A1.Oncogene · 2025Article
- Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting.British journal of cancer · 2025Article
- Mutations in CREBBP and EP300 HAT and Bromo Domains Drive Hypermutation and Predict Survival in GI Cancers Treated with Immunotherapy.Biomedicines · 2025Article
- CREBBP Mutation as a Culprit for Negative SSTR2 PET in Neuroendocrine Tumors.Molecular imaging and biology · 2025Article
- Clinical-genomic nomogram for predicting sensitivity to second-line immunotherapy for advanced non-small cell lung cancer.Translational lung cancer research · 2025Article
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Review
- Targeting KAT7 inhibits the progression of colorectal cancer.Theranostics · 2025Article
- Nanomaterial-assisted oncolytic bacteria in solid tumor diagnosis and therapeutics.Bioengineering & translational medicine · 2024Review
- Article
- FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors.ACS chemical biology · 2023Article
- Molecular targets of spermidine: implications for cancer suppression.Cell stress · 2023Article
- Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology.Seminars in radiation oncology · 2023Review
- Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors.bioRxiv : the preprint server for biology · 2023Article
- Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma.Nature communications · 2023Article
- Structural insights into p300 regulation and acetylation-dependent genome organisation.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
Despite radiation forming the curative backbone of over 50% of malignancies, there are no genomically-driven radiosensitizers for clinical use. Herein we perform in vivo shRNA screening to identify targets generally associated with radiation response as well as those exhibiting a genomic dependency. This identifies the histone acetyltransferases CREBBP/EP300 as a target for radiosensitization in combination with radiation in cognate mutant tumors. Further in vitro and in vivo studies confirm this phenomenon to be due to repression of homologous recombination following DNA damage and reproducible using chemical inhibition of histone acetyltransferase (HAT), but not bromodomain function. Selected mutations in CREBBP lead to a hyperacetylated state that increases CBP and BRCA1 acetylation, representing a gain of function targeted by HAT inhibition. Additionally, mutations in CREBBP/EP300 are associated with recurrence following radiation in squamous cell carcinoma cohorts. These findings provide both a mechanism of resistance and the potential for genomically-driven treatment.
Indexed as
Identifiers
What 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.