ArticleBMC cancer2017
Mechanism of action of trabectedin in desmoplastic small round cell tumor cells.
Article in BMC cancer, 2017. 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 10 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
10 citing papers in PubMed, 15 citations in OpenAlex.
- Paediatric therapeutic development workshop on desmoplastic small round cell tumours.British journal of cancer · 2026Review
- Review
- Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics.Frontiers in cell and developmental biology · 2024Review
- Effectiveness of irinotecan plus trabectedin on a desmoplastic small round cell tumor patient-derived xenograft.Disease models & mechanisms · 2023Article
- Small round cell sarcomas.Nature reviews. Disease primers · 2022Review
- Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy.Cancers · 2021Review
- Review
- The FUS-DDIT3 Interactome in Myxoid Liposarcoma.Neoplasia (New York, N.Y.) · 2019Article
- Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model.BMC cancer · 2018Article
- Targeting Transcription Factors for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDesmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. Current treatments are not very effective so new active drugs are needed. Trabectedin, now used as a single agent for the treatment of soft tissue sarcoma, was reported to be active in some pre-treated DSRCT patients. Using JN-DSRCT-1, a cell line derived from DSRCT expressing the EWS-WT1 fusion protein, we investigated the ability of trabectedin to modify the function of the chimeric protein, as in other sarcomas expressing fusion proteins. After detailed characterization of the EWS-WT1 transcripts structure, we investigated the mode of action of trabectedin, looking at the expression and function of the oncogenic chimera.
methodsWe characterized JN-DSRCT-1 cells using cellular approaches (FISH, Clonogenicity assay) and molecular approaches (Sanger sequencing, ChIP, GEP).
resultsJN-DSRCT-1 cells were sensitive to trabectedin at nanomolar concentrations. The cell line expresses different variants of EWS-WT1, some already identified in patients. EWS-WT1 mRNA expression was affected by trabectedin and chimeric protein binding on its target gene promoters was reduced. Expression profiling indicated that trabectedin affects the expression of genes involved in cell proliferation and apoptosis.
conclusionsThe JN-DSRCT-1 cell line, in vitro, is sensitive to trabectedin: after drug exposure, EWS-WT1 chimera expression decreases as well as binding on its target promoters. Probably the heterogeneity of chimera transcripts is an obstacle to precisely defining the molecular mode of action of drugs, calling for further cellular models of DSRCT, possibly growing in vivo too, to mimic the biological complexity of this disease.
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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.