Evidence map›Paper›PMID 35468793›Full record

ArticleJournal of translational medicine2022

FOXO transcriptional activity is associated with response to chemoradiation in EAC.

A Creemers, A P van der Zalm, A van de Stolpe, L Holtzer, M Stoffels, G K J Hooijer, E A Ebbing, H van Ooijen, A G C van Brussel, E M G Aussems-Custers and 6 more

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In one paragraph

Article in Journal of translational medicine, 2022. 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
0.2field-weighted citation impact, top 48% of its field
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, 2 citations in OpenAlex.

  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

16 authors at 4 institutions in 1 country.

A Creemers *Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
A P van der Zalm *Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-3726-1111
A van de StolpePhilips Molecular Pathway Diagnostics, Eindhoven, The Netherlands.
L HoltzerPhilips Molecular Pathway Diagnostics, Eindhoven, The Netherlands.
M StoffelsPhilips Research, Eindhoven, The Netherlands.
G K J HooijerDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
E A EbbingLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
H van OoijenPhilips Research, Eindhoven, The Netherlands.
A G C van BrusselPhilips Molecular Pathway Diagnostics, Eindhoven, The Netherlands.
E M G Aussems-CustersPhilips Research, Eindhoven, The Netherlands.
M I van Berge HenegouwenDepartment of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
M C C M HulshofDepartment of Radiotherapy, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
J J G H M BergmanDepartment of Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
S L MeijerDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
M F BijlsmaLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
H W M van LaarhovenLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. h.vanlaarhoven@amsterdamumc.nl.
Amsterdam University Medical Centers · NLPhilips (Netherlands) · NLAmsterdam Neuroscience · NLOncode Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and corresponding recurrence. Activity of six key cancer-related signaling pathways was inferred using the Bayesian inference method. When assessing pre- and post-nCRT samples, lower FOXO transcriptional activity was observed in poor nCRT responders compared to good nCRT responders (p = 0.0017). This poor responder profile was preserved in recurrences compared to matched resections (p = 0.0007). PI3K pathway activity, inversely linked with FOXO activity, was higher in CRT poor responder cell lines compared to CRT good responders. Poor CRT responder cell lines could be sensitized to CRT using PI3K inhibitors. To conclude, by using a novel method to measure signaling pathway activity on clinically available material, we identified an association of low FOXO transcriptional activity with poor response to nCRT. Targeting this pathway sensitized cells for nCRT, underlining its feasibility to select appropriate targeted therapies.

Indexed as

AdenocarcinomaEsophageal NeoplasmsBayes TheoremHumansPhosphatidylinositol 3-KinasesEsophageal adenocarcinomaNeoadjuvant chemoradiation therapyPathway analysisPredictive

Identifiers

PMID35468793
PMCPMC9036728
OpenAlexW4224861229

What OpenQuestion holds

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LicenceCC BY
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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.