ArticleMolecular cancer research : MCR2019
An Integrated Stress Response Agent that Modulates DR5-Dependent TRAIL Synergy Reduces Patient-Derived Glioma Stem Cell Viability.
Article in Molecular cancer research : MCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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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
6 citing papers in PubMed, 10 citations in OpenAlex.
- Diapause and Anoxia-Induced Quiescence Are Unique States in Embryos of the Annual Killifish,Biomolecules · 2025Article
- High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.NAR cancer · 2022Article
- Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development.International journal of molecular sciences · 2022Article
- Novel Treatment for Glioblastoma Delivered by a Radiation Responsive and Radiopaque Hydrogel.ACS biomaterials science & engineering · 2021Article
- Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness.Frontiers in oncology · 2020Review
- Treatment Strategies Based on Histological Targets against Invasive and Resistant Glioblastoma.Journal of oncology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The high incidence of glioblastoma recurrence necessitates additional therapeutic strategies. Heterogeneous populations of cells, including glioma stem cells (GSC) have been implicated in disease recurrence. GSCs are able to survive irradiation and temozolomide (TMZ) treatment due to upregulation of DNA damage pathways. One potential strategy to target treatment-resistant tumor populations may be via the integrated stress response (ISR). Modulation of the ISR pathway also allows for sensitization of treatment-resistant cells to TRAIL. We generated a novel cell-based death receptor assay to identify potent inducers of ISR-dependent DR5 expression. We used this assay to screen compounds from three commercially available libraries, and identified 1-benzyl-3-cetyl-2-methylimidazolium iodide (NH125) as a potent inducer of DR5 expression. NH125 engages the EIF2α-ATF4-CHOP axis culminating in DR5 expression at low micromolar doses. Expression of CHOP plays a critical role in NH125-mediated TRAIL synergy. Treatment of GSC with NH125 produces a marked reduction in viability when compared with other cell lines. NH125-treated GSC also synergize with lower doses of TRAIL when compared with all other cell lines tested. Transcriptional analysis of NH125-treated GSC uncovers a unique profile that involves activation of ISR and GADD45 pathways. Treatment of GSC xenografts with encapsulated PEG-PCL-NH125 leads to a sustained decrease in tumor volume. IMPLICATIONS: Taken together, these data suggest that engaging the ISR pathway represents a promising strategy to target treatment refractory GSC that have been implicated in glioblastoma recurrence.
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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.