Evidence map›Paper›PMID 40415599›Full record

ArticleMolecular oncology2025

Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma.

Piotr J Manasterski, Molly R Danks, John P Thomson, Morwenna Muir, Martin Lee, John C Dawson, Ana T Amaral, Juan Diaz-Martin, David S Moura, Javier Martin-Broto and 10 more

Abstract read
In one paragraph

Article in Molecular oncology, 2025. 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. 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

20 authors.

Piotr J ManasterskiCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Molly R DanksCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
John P ThomsonCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Morwenna MuirCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Martin LeeCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
John C DawsonCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.ORCID 0000-0001-5713-1026
Ana T AmaralInstituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
Juan Diaz-MartinInstituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
David S MouraResearch Health Institute of Fundacion Jimenez Diaz (IIS/FJD; UAM), Madrid, Spain.
Javier Martin-BrotoResearch Health Institute of Fundacion Jimenez Diaz (IIS/FJD; UAM), Madrid, Spain.
Ali AlsaadiCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Donald M SalterCentre for Genomics & Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, UK.
Ailsa J OswaldCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Graeme GrimesMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, UK.
Larry HaywardCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.
Ted R HuppCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.ORCID 0000-0003-0391-0352
Karen SisleyDivision of Clinical Medicine, School of Medicine and Population Health, The Medical School, University of Sheffield, UK.
Paul H HuangDivision of Molecular Pathology, The Institute of Cancer Research, London, UK.
Neil O CarragherCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.ORCID 0000-0001-5541-9747
Valerie G BruntonCancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, UK.ORCID 0000-0002-7778-8794

Funding

Associazione Italiana per la Ricerca sul Cancro ID #24297Cancer Research UK C56167/A29363Cancer Research UK C60521/A31343Chief Scientist Office TCS/22/12Fundacion Científica, Asociacion Espanola Contra el Cancer AECC-GEACC19007MANational Institute of Health Carlos III (ISCIII) CP24/00131NHS Research Scotland Career Researcher AwardSarcoma UK SUK06.2020Sarcoma UK SUK07.2022
6 · The paper itself

Abstract

Undifferentiated pleomorphic sarcoma (UPS) is a rare cancer with limited systemic treatment options and poor outcomes. To seek novel therapeutic interventions, we undertook mutational analysis of 20 UPS patient tumours, four established UPS cell lines and three patient-derived xenograft (PDX) models. Frequently mutated genes were uncommon; in contrast, copy number (CN) events were common with CN gain frequently observed at genes including JUN, EGFR and CDK6 and loss at WNT8B, RB1 and PTEN. Analysis of overlapping genomic changes between patient tumours and PDX models or cell lines revealed druggable events. A selected panel of drugs targeting these was analysed in in vitro UPS models demonstrating that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib is synergistic in combination with the fibroblast growth factor receptor (FGFR) inhibitor infigratinib. This was further confirmed to be efficacious in an ex vivo tumour slice model. Taken together, our results demonstrate the rationale for utilising genomic data to identify drug classes targeting druggable events in low-prevalence cancers and indicate that trametinib alone or in combination with infigratinib should be further explored for clinical UPS management.

Indexed as

Antineoplastic AgentsGenomicsSarcomaAnimalsCell Line, TumorDrug Screening Assays, AntitumorFemaleHumansMaleMiceMutationPyridonesPyrimidinonesXenograft Model Antitumor AssaysAntineoplastic AgentsPyridonesPyrimidinonestrametinibdrug screeningpatient‐derived xenografttumour slicesundifferentiated pleomorphic sarcomawhole exome sequencing

Identifiers

PMID40415599
PMCPMC12591313

What OpenQuestion holds

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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.