ArticleNature2017
Transcription elongation factors represent in vivo cancer dependencies in glioblastoma.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Temporal control of sgRNA library activation unlocks large-scale in vivo CRISPR screens.Cell reports methods · 2026Article
- Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.JCI insight · 2026Article
- ARGLU1 in Glioma: A Novel Potential Regulator of Splicing, DNA Repair, and Therapeutic Resistance.Cells · 2026Review
- Elongin B orchestrates chromatin and transcriptional programs in H3K27M-mutant diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Integrating Spatial Proteogenomics in Cancer Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma.EMBO molecular medicine · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Uncovering causal relationships in single-cell omic studies with causarray.Briefings in bioinformatics · 2026Article
- Breaking Barriers: Advancements in CNS Drug Delivery for Glioblastoma.Medical sciences (Basel, Switzerland) · 2026Review
- Single-cell RNA sequencing identifies ZBP1-dependent mechanisms in OSCC progression.Cell death & disease · 2025Article
- Synergic microRNAs suppress human glioblastoma progression by modulating clinically relevant targets.Molecular therapy. Nucleic acids · 2025Article
- Recent advancements in tissue dissociation techniques for cell manufacturing single-cell analysis and downstream processing.Stem cells translational medicine · 2025Review
- CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.Nature biotechnology · 2025Article
- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
- JMJD6-driven epigenetic activation of COL4A2 reprograms glioblastoma vascularization via integrin α1β1-dependent PI3K/MAPK signaling.Acta neuropathologica communications · 2025Article
- IWS1 positions downstream DNA to globally stimulate Pol II elongation.Nature communications · 2025Article
- An update on the clinical trial research of immunotherapy for glioblastoma.Frontiers in immunology · 2025Review
- MiR-214 promotes the antitumor effect of NK cells in colorectal cancer liver metastasis through USP27X/Bim.Cytotechnology · 2024Article
- Activity-assembled nBAF complex mediates rapid immediate early gene transcription by regulating RNA polymerase II productive elongation.Cell reports · 2024Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 10 institutions in 3 countries.
Funding
Abstract
Glioblastoma is a universally lethal cancer with a median survival time of approximately 15 months. Despite substantial efforts to define druggable targets, there are no therapeutic options that notably extend the lifespan of patients with glioblastoma. While previous work has largely focused on in vitro cellular models, here we demonstrate a more physiologically relevant approach to target discovery in glioblastoma. We adapted pooled RNA interference (RNAi) screening technology for use in orthotopic patient-derived xenograft models, creating a high-throughput negative-selection screening platform in a functional in vivo tumour microenvironment. Using this approach, we performed parallel in vivo and in vitro screens and discovered that the chromatin and transcriptional regulators needed for cell survival in vivo are non-overlapping with those required in vitro. We identified transcription pause-release and elongation factors as one set of in vivo-specific cancer dependencies, and determined that these factors are necessary for enhancer-mediated transcriptional adaptations that enable cells to survive the tumour microenvironment. Our lead hit, JMJD6, mediates the upregulation of in vivo stress and stimulus response pathways through enhancer-mediated transcriptional pause-release, promoting cell survival specifically in vivo. Targeting JMJD6 or other identified elongation factors extends survival in orthotopic xenograft mouse models, suggesting that targeting transcription elongation machinery may be an effective therapeutic strategy for glioblastoma. More broadly, this study demonstrates the power of in vivo phenotypic screening to identify new classes of 'cancer dependencies' not identified by previous in vitro approaches, and could supply new opportunities for therapeutic intervention.
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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.