Evidence map›Paper›PMID 40975876›Full record

ArticleMolecular oncology2026

Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.

Adrien M Vaquié, Davod R Shah, Eliane E S Brechbühl, Michael McNicholas, Zhaoyang Xu, John H Stockley, Laura Morcom, Diana Gold Diaz, Gemma C Girdler, Rachel V Seear and 7 more

Abstract read
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In one paragraph

Article in Molecular oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Adrien M VaquiéWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Davod R ShahWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Eliane E S BrechbühlCancer Research-UK, Cambridge Research Institute, University of Cambridge, UK.
Michael McNicholasDepartment of Oncology, Early Cancer Institute, University of Cambridge, UK.
Zhaoyang XuWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
John H StockleyWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Laura MorcomWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Diana Gold DiazWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Gemma C GirdlerWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.
Rachel V SeearDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, UK.
Gabriel BalmusDepartment of Clinical Neuroscience, UK Dementia Research Institute, University of Cambridge, UK.
Rajiv R RatanBurke Neurological Institute and Brain and Mind Research Institute, Weill Cornell Medicine, White Plains, NY, USA.
Harry BulstrodeWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.ORCID 0000-0002-3480-108X
James A NathanDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, UK.ORCID 0000-0002-0248-1632
Manav PathaniaDepartment of Oncology, Early Cancer Institute, University of Cambridge, UK.
Kevin M BrindleCancer Research-UK, Cambridge Research Institute, University of Cambridge, UK.
David H RowitchWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, UK.ORCID 0000-0002-0079-0060

Funding

Dr Miriam and Sheldon G. Adelson Medical Research FoundationEuropean Research Council Advanced Grant 789054NIHR Cambridge Biomedical Research Centre NIHR203312Swiss National Science foundation (SNSF) P2FRP3_188056Wellcome Trust 223011
6 · The paper itself

Abstract

Glioma stem cells (GSCs) from this aggressive brain cancer have been subject to nononcogene addiction therapeutic strategies, in particular targeting iron and cholesterol metabolic pathways. In this study, we show the small molecule Adaptaquin (AQ) has anti-GSC effects while sparing neurons, mature oligodendrocytes and astrocytes. Transcriptomic analysis of AQ-treated GSCs showed dramatic upregulation of iron transport genes and downregulation of genes involved in cholesterol biosynthesis. Indeed, we found cytotoxic effects of AQ on GSCs were potentiated when combined with the iron chelator deferoxamine (DFO). Notably, these effects were independent of PHD2 and HIF1α regulation, indicating a distinct pathway of action. Furthermore, we observed that the heme analogue, hemin, protects GSCs from AQ-mediated cell death, suggesting the presence of a functional heme transporter in GSCs, an observation confirmed by uptake of heme analogues. Importantly, we found that AQ treatment alone or in combination with iron chelators impaired cholesterol homeostasis in GSCs, leading to mitochondrial fragmentation and cell death. These findings suggest AQ in combination with iron chelators results in lethal disruption of cholesterol metabolism in glioma stem cells.

Indexed as

Brain NeoplasmsCholesterolGliomaIronNeoplastic Stem CellsAnimalsCell Line, TumorDeferoxamineHumansIron Chelating AgentsCholesterolDeferoxamineIronIron Chelating AgentsAdaptaquincholesteroldeferoxamineglioma stem cellsironnononcogene addiction

Identifiers

PMID40975876
PMCPMC7618758

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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.