ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Trabectedin Inhibits EWS-FLI1 and Evicts SWI/SNF from Chromatin in a Schedule-dependent Manner.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07328425 (Phase II Study of Lurbinectedin and Irinotecan in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor), which is not on this map. Cited by 35 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.
Phase II Study of Lurbinectedin and Irinotecan in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT)
Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial.Nature medicine · 2026Trial
- Crystal Structure of Trabectedin-DNA Complex.Journal of molecular biology · 2026Article
- Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma.Translational oncology · 2026Article
- Mithramycin alters EWS::FLI1 DNA binding and RNA polymerase II processivity to inhibit nascent transcription.Nature communications · 2026Article
- Dynamic regulation of endogenous transcription factor hubs at single-molecule resolution.bioRxiv : the preprint server for biology · 2026Article
- DCMiC: a double-cylinder micro-chamber platform for high-throughput drug screening and modeling of microenvironmental resistance in Ewing sarcoma.Lab on a chip · 2026Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Ewing Sarcoma, Desmoplastic Small Round Cell Tumor, and Other Round Cell Sarcomas.Hematology/oncology clinics of North America · 2025Review
- Epigenetic roles of chromatin remodeling complexes in bone biology and the pathogenesis of bone‑related disease (Review).International journal of molecular medicine · 2025Review
- Exploiting divergent mechanisms of trabectedin for bone tumors.Molecular therapy. Oncology · 2025Article
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.Molecular therapy. Oncology · 2024Article
- Prion-like domain mediated phase separation of ARID1A promotes oncogenic potential of Ewing's sarcoma.Nature communications · 2024Article
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.Cellular and molecular life sciences : CMLS · 2024Article
- Children's Oncology Group's 2023 blueprint for research: Bone tumors.Pediatric blood & cancer · 2023Article
- Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.International journal of molecular sciences · 2023Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- High-throughput approaches to uncover synergistic drug combinations in leukemia.SLAS discovery : advancing life sciences R & D · 2023Article
- Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies.Cancers · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe successful clinical translation of compounds that target specific oncogenic transcription factors will require an understanding of the mechanism of target suppression to optimize the dose and schedule of administration. We have previously shown trabectedin reverses the gene signature of the EWS-FLI1 transcription factor. In this report, we establish the mechanism of suppression and use it to justify the reevaluation of this drug in the clinic in patients with Ewing sarcoma.
resultsTrabectedin evicts the SWI/SNF chromatin-remodeling complex from chromatin and redistributes EWS-FLI1 in the nucleus leading to a marked increase in H3K27me3 and H3K9me3 at EWS-FLI1 target genes. These effects only occur at high concentrations of trabectedin leading to suppression of EWS-FLI1 target genes and a loss of cell viability.
conclusionsThese data provide the justification to evaluate trabectedin in the clinic on a short infusion schedule in combination with low-dose irinotecan with
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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.