Evidence map›Paper›PMID 39423824›Full record

ArticleStem cell reports2024

Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex.

Audrey Burban, Ahmad Sharanek, Aldo Hernandez-Corchado, Hamed S Najafabadi, Vahab D Soleimani, Arezu Jahani-Asl

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Audrey BurbanDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology, McGill University, 5100 de Maisonneuve Boulevard West, Montréal, QC H4A 3T2, Canada.
Ahmad SharanekDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology, McGill University, 5100 de Maisonneuve Boulevard West, Montréal, QC H4A 3T2, Canada.
Aldo Hernandez-CorchadoDepartment of Medicine, Division of Experimental Medicine, McGill University, 1001 Decarie Boulevard, Montréal, QC H4A 3J1, Canada; Department of Human Genetics, McGill University, 3640 Rue University, Montréal, QC H3A OC7, Canada.
Hamed S NajafabadiDepartment of Medicine, Division of Experimental Medicine, McGill University, 1001 Decarie Boulevard, Montréal, QC H4A 3J1, Canada; Department of Human Genetics, McGill University, 3640 Rue University, Montréal, QC H3A OC7, Canada.
Vahab D SoleimaniLady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada; Department of Human Genetics, McGill University, 3640 Rue University, Montréal, QC H3A OC7, Canada; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Arezu Jahani-AslDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada; Gerald Bronfman Department of Oncology, McGill University, 5100 de Maisonneuve Boulevard West, Montréal, QC H4A 3T2, Canada; Cancer Therapeutic and Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. Electronic address: arezu.jahani@uottawa.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain tumor stem cells (BTSCs) are a population of self-renewing malignant stem cells that play an important role in glioblastoma tumor hierarchy and contribute to tumor growth, therapeutic resistance, and tumor relapse. Thus, targeting of BTSCs within the bulk of tumors represents a crucial therapeutic strategy. Here, we report that edaravone is a potent drug that impairs BTSCs in glioblastoma. We show that edaravone inhibits the self-renewal and growth of BTSCs harboring a diverse range of oncogenic mutations without affecting non-oncogenic neural stem cells. Global gene expression analysis revealed that edaravone significantly alters BTSC transcriptome and attenuates the expression of a large panel of genes involved in cell cycle progression, stemness, and DNA repair mechanisms. Mechanistically, we discovered that edaravone directly targets Notchless homolog 1 (NLE1) and impairs Notch signaling pathway, alters the expression of stem cell markers, and sensitizes BTSC response to ionizing radiation (IR)-induced cell death. Importantly, we show that edaravone treatment in preclinical models delays glioblastoma tumorigenesis, sensitizes their response to IR, and prolongs the lifespan of animals. Our data suggest that repurposing of edaravone is a promising therapeutic strategy for patients with glioblastoma.

Indexed as

Brain NeoplasmsEdaravoneGlioblastomaNeoplastic Stem CellsReceptor, Notch1AnimalsCell Line, TumorCell ProliferationCell Self RenewalGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMiceSignal TransductionEdaravoneIntracellular Signaling Peptides and ProteinsReceptor, Notch1drug repurposingedaravoneionizing radiationNLE1/Notch1 signallingstemness

Identifiers

PMID39423824
PMCPMC11589194

What OpenQuestion holds

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Registered trials

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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.