Evidence map›Paper›PMID 41430412›Full record

ArticleScientific reports2025

Navitoclax acts synergistically with irradiation to induce apoptosis in preclinical models of H3K27M-altered diffuse midline glioma.

Ashley Vardon, Scott Haston, Hiba Hamdi, Grace Cooksley, Romain Guiho, Diana Carvalho, Rebecca Carter, Jessica Katherine Rowena Boult, Daniel Gharai, Ielyaas Cloete and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. 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. 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

27 authors.

Ashley VardonDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Scott HastonDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Hiba HamdiDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Grace CooksleyDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Romain GuihoDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Diana CarvalhoBrain Tumour Research Centre of Excellence, Division of Molecular Pathology, Institute of Cancer Research, London, UK.
Rebecca CarterUCL Cancer Institute, University College London, Paul O'Gorman Building, London, UK.
Jessica Katherine Rowena BoultDivision of Radiotherapy and Imaging, Institute of Cancer Research, London, UK.
Daniel GharaiDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Ielyaas CloeteDepartment of Medical Physics and Biomedical Engineering, University College London, London, UK.
James GreyDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
John AppsInstitute of Cancer and Genomic Medicine, University of Birmingham, Birmingham, UK.
Daohong ZhouDepartment of Biochemistry and Structural Biology and Center for Innovative Drug Discovery, University of Texas Health San Antonio, San Antonio, USA.
Guangrong ZhengUniversity of Florida Health Cancer Center, University of Florida, Gainesville, USA.
Ramón Martínez-MáñezInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, València, Spain.
Mark Francis LythgoeUCL Cancer Institute, University College London, Paul O'Gorman Building, London, UK.
Laura Kate DonovanDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Angel Montero CarcabosoSJD Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Institut de Recerca Sant Joan de Deu (IRSJD), Barcelona, Spain.
Owen WilliamsDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Ying HongInfection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Paula AlexandreDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Jesus GilMRC Laboratory of Medical Sciences (LMS), Du Cane Road, London, W12 0NN, UK.
Jamie Adam DeanDepartment of Medical Physics and Biomedical Engineering, University College London, London, UK.
David MichodDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Chris JonesBrain Tumour Research Centre of Excellence, Division of Molecular Pathology, Institute of Cancer Research, London, UK.
Darren HargraveDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK.
Juan-Pedro Martinez-BarberaDevelopmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK. j.martinez-barbera@ucl.ac.uk.

Funding

Brain Tumour Charity GN-000382, GN-000707, GN-000522 and GN-000728Brain Tumour Research DRCRPG-Nov21\100002Cancer Research UK C15075/A28647Cancer Research UK C54322/A27725Cancer Research UK C54322/A27727Cancer Research UK C7893/A28990Cancer Research UK C7893/A28990).Cancer Research UK DRCRPG-Nov21\100002Cancer Research UK RRNPSF-Mar22\100002Great Ormond Street Hospital Charity V5119Medical Research Scotland MC_U120085810
6 · The paper itself

Abstract

Diffuse midline gliomas (DMGs) with histone H3K27M mutations represent a devastating paediatric brain cancer characterised by abysmal prognosis and limited treatment options. The only approved treatment is radiotherapy (RT), but most of the tumours relapse with fatal consequences. The effects of RT remain unknown because patients are not biopsied during treatment. Here, we sought to investigate whether irradiation leads to senescence induction in DMG and explore the efficacy of senolytics. We show that ionising radiation induces senescence in various H3K27M-altered DMG cell lines. Senescence induction is demonstrated by immunocytochemistry, RNA-sequencing and analysis of SASP factors by ELISA. Through testing several senolytic compounds, we identify that Bcl2 family inhibitors (e.g., Navitoclax) act as potent senolytics, driving senescent DMG cells into apoptosis, primarily via Bcl-xL inhibition. Reinforcing these findings, proteolysis-targeting chimeras (PROTACs) targeting Bcl-xL and galacto-conjugated Navitoclax (Nav-Gal) also exhibit strong senolytic activity against senescent DMG cancer cells. Finally, we show that a combination of irradiation with Navitoclax enhances cancer cell apoptosis in an orthotopic xenograft DMG model. Together, the data demonstrate that ionising irradiation leads to senescence induction in H3K27M-altered human DMG cell lines, making them particularly sensitive to apoptosis through Bcl-xL inhibition.

Indexed as

Aniline CompoundsAntineoplastic AgentsApoptosisBrain NeoplasmsGliomaHistonesSulfonamidesAnimalsbcl-X ProteinCell Line, TumorCellular SenescenceHumansMiceMutationXenograft Model Antitumor AssaysAniline CompoundsAntineoplastic Agentsbcl-X ProteinHistonesnavitoclaxSulfonamidesBcl-xLBH3-mimeticsCellular senescenceH327M-altered diffuse midline gliomaSenolytic therapy

Identifiers

PMID41430412
PMCPMC12749289

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.