Evidence map›Paper›PMID 32810173›Full record

ArticlePloS one2020

3D imaging of colorectal cancer organoids identifies responses to Tankyrase inhibitors.

Luned M Badder, Andrew J Hollins, Bram Herpers, Kuan Yan, Kenneth B Ewan, Mairian Thomas, Jennifer R Shone, Delyth A Badder, Marc Naven, Kevin E Ashelford and 11 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Engineered organoids for biomedical applications.Advanced drug delivery reviews · 2023
    Review
  6. Article
  7. Article
  8. Review
  9. Everything You Always Wanted to Know About Organoid-Based Models (and Never Dared to Ask).Cellular and molecular gastroenterology and hepatology · 2022
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Patient-Derived Organoids as a Model for Cancer Drug Discovery.International journal of molecular sciences · 2021
    Review
  15. 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

21 authors at 4 institutions in 2 countries.

Luned M BadderCardiff University School of Biosciences, Cardiff, Wales, United Kingdom.
Andrew J HollinsCardiff University School of Biosciences, Cardiff, Wales, United Kingdom.
Bram HerpersOcellO B.V., Leiden, The Netherlands.
Kuan YanOcellO B.V., Leiden, The Netherlands.ORCID 0000-0003-4143-3569
Kenneth B EwanCardiff University School of Biosciences, Cardiff, Wales, United Kingdom.
Mairian ThomasCellesce Ltd, Cardiff Medicentre, Heath Park, Cardiff, United Kingdom.
Jennifer R ShoneCardiff University School of Biosciences, Cardiff, Wales, United Kingdom.
Delyth A BadderCellular Pathology Department, University Hospital for Wales, Cardiff, United Kingdom.
Marc NavenDivision of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Kevin E AshelfordDivision of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Rachel HargestDepartment of Colorectal Surgery, University Hospital of Wales, Cardiff, United Kingdom.
Alan R ClarkeEuropean Cancer Stem Cell Research Institute (ECSCRI), Cardiff University, Cardiff, Wales, United Kingdom.
Christina EsdarBiopharma, Merck Healthcare KGaA, Research & Development, Darmstadt, Germany.
Hans-Peter BuchstallerBiopharma, Merck Healthcare KGaA, Research & Development, Darmstadt, Germany.
J Mark TreherneCellesce Ltd, Cardiff Medicentre, Heath Park, Cardiff, United Kingdom.
Sylvia BojHubrecht Organoid Technology, Utrecht, The Netherlands.
Bahar RamezanpourHubrecht Organoid Technology, Utrecht, The Netherlands.
Dirk WienkeBiopharma, Merck Healthcare KGaA, Research & Development, Darmstadt, Germany.
Leo S PriceOcellO B.V., Leiden, The Netherlands.
Paul H ShawVelindre Cancer Centre, Cardiff, Wales, United Kingdom.
Trevor C DaleEuropean Cancer Stem Cell Research Institute (ECSCRI), Cardiff University, Cardiff, Wales, United Kingdom.ORCID 0000-0002-4880-9963
Cardiff University · GBMerck (Germany) · DEUniversity Hospital of Wales · GBVelindre Cancer Centre · GB

Funding

Cancer Research UK C1295/A15937H
6 · The paper itself

Abstract

Aberrant activation of the Wnt signalling pathway is required for tumour initiation and survival in the majority of colorectal cancers. The development of inhibitors of Wnt signalling has been the focus of multiple drug discovery programs targeting colorectal cancer and other malignancies associated with aberrant pathway activation. However, progression of new clinical entities targeting the Wnt pathway has been slow. One challenge lies with the limited predictive power of 2D cancer cell lines because they fail to fully recapitulate intratumoural phenotypic heterogeneity. In particular, the relationship between 2D cancer cell biology and cancer stem cell function is poorly understood. By contrast, 3D tumour organoids provide a platform in which complex cell-cell interactions can be studied. However, complex 3D models provide a challenging platform for the quantitative analysis of drug responses of therapies that have differential effects on tumour cell subpopulations. Here, we generated tumour organoids from colorectal cancer patients and tested their responses to inhibitors of Tankyrase (TNKSi) which are known to modulate Wnt signalling. Using compounds with 3 orders of magnitude difference in cellular mechanistic potency together with image-based assays, we demonstrate that morphometric analyses can capture subtle alterations in organoid responses to Wnt inhibitors that are consistent with activity against a cancer stem cell subpopulation. Overall our study highlights the value of phenotypic readouts as a quantitative method to asses drug-induced effects in a relevant preclinical model.

Indexed as

AdultAnimalsAntineoplastic AgentsColorectal NeoplasmsEnzyme InhibitorsFemaleHumansImaging, Three-DimensionalMaleMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsOrganoidsTankyrasesAntineoplastic AgentsEnzyme InhibitorsTankyrases

Identifiers

PMID32810173
PMCPMC7433887
OpenAlexW3053764042

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.