Evidence map›Paper›PMID 41397959›Full record

ArticleNature communications2025

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.

George L Joun, Emma G Kempe, Brianna Chen, Jayden R Sterling, Ramzi H Abbassi, Dana Friess, Matthew Singleton, Chandra Choudhury, Oana C Marian, W Daniel du Preez and 27 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026
    Review
  4. Review
  5. 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

37 authors.

George L JounSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Emma G KempeSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0009-0004-8470-6402
Brianna ChenSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Jayden R SterlingSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Ramzi H AbbassiSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-8007-4648
Dana FriessQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-2526-4451
Matthew SingletonQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Chandra ChoudhuryQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Oana C MarianSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-5629-7884
W Daniel du PreezSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Ariadna RecasensSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Teleri ClarkCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Tian Y DuCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-0674-361X
Jason K K LowSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-0862-0012
Hani KimCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Pengyi YangCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-1098-3138
Jasmine KhorSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Monira HoqueSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Dinesh C IndurthiSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-8837-5883
Mani KuchibhotlaCentre for Child Health Research, Medical School, University of Western Australia, Crawley, WA, Australia.
Ranjith PalanisamyCentre for Child Health Research, Medical School, University of Western Australia, Crawley, WA, Australia.
William T JorgensenSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Andrew P MontgomerySchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
Jennifer R BakerSchool of Science, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Sarah L HigginbottomArto Hardy Family Biomedical Innovation Hub, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
Eva Tomaskovic-CrookSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Jeremy M CrookSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-6415-1639
Lipin LooCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-4112-1816
Bryan W DayQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
G Gregory NeelyCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-1957-9732
Ernesto GuccioneDepartment of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-7764-5307
Terrance G JohnsCentre for Child Health Research, Medical School, University of Western Australia, Crawley, WA, Australia.
Michael KassiouSchool of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-6655-0529
Yuchen FengSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Lachlan HarrisQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Anthony S DonSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-1655-1184
Lenka MunozSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. lenka.munoz@sydney.edu.au.ORCID http://orcid.org/0000-0002-7625-5646

Funding

Department of Health | National Health and Medical Research Council (NHMRC) APP1153961Department of Health | National Health and Medical Research Council (NHMRC) APP2003150
6 · The paper itself

Abstract

Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identify that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, results in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.

Indexed as

Brain NeoplasmsDrug Resistance, NeoplasmGlioblastomaHistone-Lysine N-MethyltransferaseAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalCholesterolGene Expression Regulation, NeoplasticHistonesHumansLipid MetabolismMetabolic ReprogrammingMethylationMiceAntineoplastic AgentsCholesterolHistone-Lysine N-MethyltransferaseHistonesPRDM9 protein, human

Identifiers

PMID41397959
PMCPMC12705669

What OpenQuestion holds

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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 OpenQuestion graph.