Evidence map›Paper›PMID 35139880›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer.

Zaheer Ali, Malin Vildevall, Gabriela Vazquez Rodriguez, Decky Tandiono, Ioannis Vamvakaris, Georgios Evangelou, Georgios Lolas, Konstantinos N Syrigos, Alberto Villanueva, Michael Wick and 5 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
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  8. Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026
    Review
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  14. Preclinical models in the study of lymph node metastasis.Journal of Zhejiang University. Science. B · 2025
    Review
  15. Article
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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

15 authors at 5 institutions in 4 countries.

Zaheer AliBioReperia AB, Linköping, Sweden.
Malin VildevallBioReperia AB, Linköping, Sweden.
Gabriela Vazquez RodriguezBioReperia AB, Linköping, Sweden.
Decky TandionoBioReperia AB, Linköping, Sweden.
Ioannis VamvakarisPathology Department, Athens Chest Hospital "Sotiria", Athens, Greece.
Georgios Evangelou3rd Department of Internal Medicine and Laboratory, National & Kapodistrian University of Athens, Athens, Greece.
Georgios Lolas3rd Department of Internal Medicine and Laboratory, National & Kapodistrian University of Athens, Athens, Greece.
Konstantinos N Syrigos3rd Department of Internal Medicine and Laboratory, National & Kapodistrian University of Athens, Athens, Greece.
Alberto VillanuevaProgram Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Michael WickXenoSTART, San Antonio, TX, USA.
Shenga OmarDivision of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Campus US, Entrance 68, Pl. 08, SE-58185, Linköping, Sweden.
Anna ErkstamBioReperia AB, Linköping, Sweden.
Julia SchuelerCharles River Laboratories, Freiburg, Germany.
Anna FahlgrenBioReperia AB, Linköping, Sweden.
Lasse D JensenBioReperia AB, Linköping, Sweden. lasse.jensen@liu.se.ORCID http://orcid.org/0000-0003-2338-357X
Linköping University · SENational and Kapodistrian University of Athens · GRBellvitge University Hospital · ESCharles River Laboratories (Germany) · DESotiria General Hospital · GR

Funding

h2020 marie skłodowska-curie actions 3D-NEONET
6 · The paper itself

Abstract

backgroundAccurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days.

methodsUsing a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients.

resultsThe resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days.

conclusionsWe conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.

Indexed as

AnimalsCarcinoma, Non-Small-Cell LungDisease Models, AnimalHumansLung NeoplasmsLymph NodesNeoplasm MetastasisTreatment OutcomeXenograft Model Antitumor AssaysZebrafishCancerDisseminationDrug responseLymph nodeMetastasisPDXXenograftZebrafishZTX

Identifiers

PMID35139880
PMCPMC8827197
OpenAlexW4210886590

What OpenQuestion 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 OpenQuestion graph.