ArticleMolecular cancer2024
Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- BAF complex-independent gene activation by SS18::SSX.bioRxiv : the preprint server for biology · 2026Article
- Aging-associated immune and stromal programs mark interferon- and remodeling-linked spatial contexts in psoriatic skin.Frontiers in immunology · 2026Article
- Heterogeneous Folding Intermediates Govern the Conformational Pathway of the RNA Recognition Motif Domain of the Ewing Sarcoma Protein.Biomolecules · 2025Article
- Modeling CIC::DUX4 sarcoma reveals oncogene-mediated MHCI-dependent immune evasion.Molecular cancer · 2025Article
- Clinical characteristics and target exploration via scRNA-seq and high-throughput drug screening of FOXO1 fusion positive rhabdomyosarcoma.Pediatric surgery international · 2025Article
- Review
- The Double Life of microRNAs in Bone Sarcomas: Oncogenic Drivers and Tumor Suppressors.International journal of molecular sciences · 2025Review
- RNA-based therapies for colorectal cancer: targeting the β-catenin pathway via microbiota -modulated miRNAs.Frontiers in molecular biosciences · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Ewing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.
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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.