Evidence map›Paper›PMID 32358191›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma.

Kruttika Bhat, Mohammad Saki, Erina Vlashi, Fei Cheng, Sara Duhachek-Muggy, Claudia Alli, Garrett Yu, Paul Medina, Ling He, Robert Damoiseaux and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% of its field
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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  13. Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Effects of dopamine receptor antagonists and radiation on mouse neural stem/progenitor cells.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2024
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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

17 authors at 1 institution in 1 country.

Kruttika BhatDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Mohammad SakiDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Erina VlashiDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Fei ChengDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Sara Duhachek-MuggyDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Claudia AlliDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Garrett YuDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Paul MedinaDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Ling HeDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0002-8692-7530
Robert DamoiseauxJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095.ORCID 0000-0001-9355-9564
Nathan R ZemkeDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095.
Phioanh Leia NghiemphuJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.
Timothy F CloughesyJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.
Linda M LiauJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.ORCID 0000-0002-4053-0052
Harley I KornblumJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.
Frank PajonkDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; pajonk@ucla.edu.ORCID 0000-0003-4067-9751
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Glioblastoma, Glioblastoma Stem Cells and RadiotherapyR01CA200234 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2016 to 2020
$1.8M
Erythropoietin and Breast Cancer Stem CellsR01CA161294 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2012 to 2016
$1.6M
The 26S Proteasome in Cancer Stem CellsR01CA137110 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2009 to 2013
$1.6M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA137110NCI NIH HHS R01 CA161294NCI NIH HHS R01 CA200234
6 · The paper itself

Abstract

Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

Indexed as

PhenotypeAnimalsbeta CateninBrain NeoplasmsDisease Models, AnimalDopamine AntagonistsGene Expression Regulation, NeoplasticGlioblastomaGliomaGlycogen Synthase Kinase 3MiceMice, Inbred C57BLMice, Inbred NODMice, SCIDRadiation ToleranceReceptors, Dopaminebeta CateninCTNNB1 protein, mouseDopamine AntagonistsGlycogen Synthase Kinase 3Receptors, DopamineRNA, MessengerSox2 protein, mouseSOXB1 Transcription FactorsTrifluoperazinededifferentiationdopamine receptor antagonistglioblastomaglioma-initiating cellsradiation

Identifiers

PMID32358191
PMCPMC7245100
OpenAlexW3021221826

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.