ArticleMolecular cancer therapeutics2020
CDK9 Blockade Exploits Context-dependent Transcriptional Changes to Improve Activity and Limit Toxicity of Mithramycin for Ewing Sarcoma.
Article in Molecular cancer therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 27 citations in OpenAlex.
- Mithramycin alters EWS::FLI1 DNA binding and RNA polymerase II processivity to inhibit nascent transcription.Nature communications · 2026Article
- Endogenous EWSR1 Exists in Two Visual Modalities That Reflect Its Associations with Nucleic Acids and Concentration at Sites of Active Transcription.Molecular and cellular biology · 2024Article
- CRISPR-Cas9 knockout screening identifies KIAA1429 as an essential gene in Ewing sarcoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Ewing sarcoma and related FET family translocation-associated round cell tumors: A century of clinical and scientific progress.Genes, chromosomes & cancer · 2022Article
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Mithramycin delivery systems to develop effective therapies in sarcomas.Journal of nanobiotechnology · 2021Article
- Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas.Journal of clinical medicine · 2021Article
- CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor-targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1-targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC
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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.