Evidence map›Paper›PMID 39528460›Full record

ArticleNature communications2024

Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts.

Umberto Perron, Elena Grassi, Aikaterini Chatzipli, Marco Viviani, Emre Karakoc, Lucia Trastulla, Lorenzo M Brochier, Claudio Isella, Eugenia R Zanella, Hagen Klett and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

19 authors.

Umberto Perron *Human Technopole, Milano, Italy.
Elena Grassi *Candiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0003-1066-927X
Aikaterini Chatzipli *Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Marco VivianiCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0003-4698-8870
Emre KarakocWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Lucia TrastullaHuman Technopole, Milano, Italy.
Lorenzo M BrochierHuman Technopole, Milano, Italy.ORCID 0009-0002-5306-094X
Claudio IsellaCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0003-0679-4756
Eugenia R ZanellaCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.
Hagen KlettCharles River Germany GmbH, Freiburg, Germany.
Ivan MolinerisDepartment of Life Sciences and Systems Biology, University of Torino, Torino, Italy.ORCID 0000-0003-2102-0804
Julia SchuelerCharles River Germany GmbH, Freiburg, Germany.ORCID 0000-0003-1984-7343
Manel EstellerJosep Carreras Leukemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.ORCID 0000-0003-4490-6093
Enzo MedicoCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0002-3917-2438
Nathalie ConteEuropean Molecular Biology Laboratory European Bioinformatics Institute, Cambridge, UK.
Ultan McDermottWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID 0000-0001-9032-4700
Livio TrusolinoCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy. livio.trusolino@ircc.it.ORCID 0000-0002-6379-3365
Andrea BertottiCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy. andrea.bertotti@ircc.it.ORCID 0000-0001-8196-7608
Francesco IorioHuman Technopole, Milano, Italy. francesco.iorio@fht.org.ORCID 0000-0001-7063-8913

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 20697Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 21091Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 22795Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 22802Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 28772
6 · The paper itself

Abstract

Patient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cancer cell lines (CCLs) and organoids - in terms of structural complexity, heterogeneity, and stromal interactions. Here, we characterise 231 colorectal cancer PDXs at the genomic, transcriptomic, and epigenetic levels, along with their response to cetuximab, an EGFR inhibitor used clinically for metastatic colorectal cancer. After evaluating the PDXs' quality, stability, and molecular concordance with publicly available patient cohorts, we present results from training, interpreting, and validating the integrative ensemble classifier CeSta. This model takes in input the PDXs' multi-omic characterisation and predicts their sensitivity to cetuximab treatment, achieving an area under the receiver operating characteristics curve > 0.88. Our study demonstrates that large PDX collections can be leveraged to train accurate, interpretable drug sensitivity models that: (1) better capture patient-derived therapeutic biomarkers compared to models trained on CCL data, (2) can be robustly validated across independent PDX cohorts, and (3) could contribute to the development of future therapeutic biomarkers.

Indexed as

CetuximabColorectal NeoplasmsXenograft Model Antitumor AssaysAnimalsAntineoplastic Agents, ImmunologicalBiomarkers, TumorCell Line, TumorErbB ReceptorsFemaleHumansMiceAntineoplastic Agents, ImmunologicalBiomarkers, TumorCetuximabErbB Receptors

Identifiers

PMID39528460
PMCPMC11555063

What OpenQuestion holds

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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.