Evidence map›Paper›PMID 41986321›Full record

ArticleCell death & disease2026

PRMT5 inhibition impairs Fanconi Anemia pathway-mediated homologous recombination and enhances the antitumor efficacy of Temozolomide in glioblastoma.

Shumpei Onishi, Sridharan Jayamohan, Ashis Chowdhury, Sarah Rivas, Yoshihiro Otani, Celine Ertekin, Jean-Paul Bryant, Sara A Murphy, Kimberly A Rivera-Caraballo, Stuart Walbridge and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

24 authors.

Shumpei Onishi *Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4156-6540
Sridharan Jayamohan *Department of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX, USA.
Ashis Chowdhury *Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Sarah RivasSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Yoshihiro OtaniDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
Celine ErtekinSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Jean-Paul BryantSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Sara A MurphyGeorgia Cancer Center, Augusta University Medical Center, Augusta, GA, USA.ORCID http://orcid.org/0000-0003-2722-0081
Kimberly A Rivera-CaraballoGeorgia Cancer Center, Augusta University Medical Center, Augusta, GA, USA.ORCID http://orcid.org/0000-0001-9275-7286
Stuart WalbridgeSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Bayu SisayCancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Dragan MaricFlow and Imaging Cytometry Core Facility, NINDS, NIH, Bethesda, MD, USA.
Abdel ElkahlounCancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Kory JohnsonBioinformatics Core, Information Technology Program, NINDS, NIH, Bethesda, MD, USA.
Desmond A BrownSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
John D HeissSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Ashish H ShahSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Tae Jin LeeDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
Sangamesh G KumbarDepartment of Growth and Development, College of Dentistry, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0001-7672-4783
Ji Young YooDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA.
Andrew J BrennerMays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA.
Balveen KaurGeorgia Cancer Center, Augusta University Medical Center, Augusta, GA, USA.
Gangadhara R SareddyDepartment of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-9977-3932
Yeshavanth Kumar Banasavadi-SiddegowdaSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. yesh.banasavadisiddegowda@nih.gov.ORCID http://orcid.org/0000-0002-4730-6918

Funding

Enhanced Viro-Immunotherapy for Breast Cancer Brain MetastasisR01CA276942 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Ji Young Yoo · 2023 to 2026
$2.2M
IGF1R-targeted oncolytic herpes simplex viral therapy for GlioblastomaR21NS123685 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI YOO, JI YOUNG · 2022 to 2023
$405k
U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01NS106173-01A1U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA276942U.S. Department of Health & Human Services | National Institutes of Health (NIH) R21NS123685U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program
6 · The paper itself

Abstract

Despite multimodal therapy of surgical resection, radiation, and chemotherapy, glioblastoma patients show a dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma, and its inhibition imparts an anti-tumor effect. Tumor cells invariably develop resistance to Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma. However, the mechanistic role of PRMT5 in treatment-resistant glioblastoma is unknown. Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment. We found that PRMT5 inhibition increased the cytotoxic effect of TMZ in GSCs. Unbiased transcriptomic profiling revealed negative enrichment of DNA damage repair pathways, with prominent suppression of the Fanconi anemia (FA) pathway. PRMT5 inhibition abrogated the TMZ-induced G2/M cell cycle arrest. Importantly, combination treatment increased the DNA double-strand breaks (γH2AX foci) and enhanced the DNA damage (comet assay). Specifically, the LLY-283 treatment blocked the FA pathway-mediated homologous recombination repair in GSCs. In vivo, the LLY-283 and TMZ combination significantly curbs tumor growth and prolongs the survival of tumor-bearing mice. Furthermore, compared to monotherapy, there was a significant reduction in the proliferation marker Ki-67, while the apoptosis marker cleaved caspase 3 and the DNA damage response marker γH2AX were upregulated. Collectively, these findings identify PRMT5 as a critical regulator of the FA pathway in glioblastoma and demonstrate that PRMT5 inhibition potentiates TMZ efficacy by disrupting FA-dependent homologous recombination repair, indicating that the combination of PRMT5 inhibition and TMZ could be a novel therapeutic strategy for glioblastoma.

Indexed as

Brain NeoplasmsFanconi AnemiaGlioblastomaHomologous RecombinationProtein-Arginine N-MethyltransferasesTemozolomideAnimalsAntineoplastic Agents, AlkylatingApoptosisCell Line, TumorHumansMiceMice, NudeSignal TransductionXenograft Model Antitumor AssaysAntineoplastic Agents, AlkylatingPRMT5 protein, humanProtein-Arginine N-MethyltransferasesTemozolomide

Identifiers

PMID41986321
PMCPMC13194734

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.