The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
Open accessAbstract
In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the "living biobank" agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.
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“‘living biobanks’ can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers124,151,176–178, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases179”
From Human disease models in drug development (2023) · cites this paper as [151]
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“Organoids are ideally suited for FPM due to their ease of establishment, similarity with the tissue of origin and tractability158,167 and have been deployed to identify therapeutic leads in a number of tumors168, including rare cancers that tend to be understudied and poorly characterized at the molecular level16,151,169,170.”
From Organoids (2022) · cites this paper as [169]
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“Recent studies using in vitro organoids grown from different intestinal tumors [33, 34] showed a strong correlation, functionally and molecularly with their primary tissue counterparts, providing a strong argument in favor of the potential for in vitro systems to model intestinal disease.”
From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [34]
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“In short, the wild-type human colon organoid line P26n, as previously described in Van De Wetering et al. (2015) was cultured in domes of Cultrex Pathclear Reduced Growth Factor Basement Membrane Extract (BME) (3533-001; Amsbio).”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as Van De Wetering et al. (2015)
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“broad clinical implementation of patient-specific disease models, such as PDOs, is currently hindered by low efficiencies in PDO establishment (60–70% success rate on average although, for some tissues, up to 90% have been reported for intestinal organoids151) as well as lengthy generation times and expansion procedures”
From Human disease models in drug development (2023) · cites this paper as [151]
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“Patient-derived tumor organoid (a.k.a. tumoroid) biobanks can be established from biopsies, surgical resections2,3, and even from Pap brushes4.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [3]
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“The reconstituted TME model recapitulates not only the genetic and phenotypic features of a tumor but also models the functional response of a patient to therapeutic agents [389, 390].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [389]
In the citing paper
“3D patient-derived tumor models of CRC (i.e., organoid and spheroid cultures) allow maintenance and expansion of functionally relevant cell subfractions and harbor the patients' individual genetic lesions (Ishiguro et al., 2017;van de Wetering et al., 2015).”
From Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer (2021) · cites this paper as van de Wetering et al., 2015
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“Furthermore, with recent technological advancements (e.g. organoid models and conditionally reprogrammed cell lines), a new generation of cancer cell models is being derived to allow full representation of the histopathological and molecular diversity of tumours (37–42).”
From Cell Model Passports-a hub for clinical, genetic and functional datasets of preclinical cancer models (2019) · cites this paper as [37]
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Cites
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A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
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Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
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Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196
Self-citationBatlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769
Self-citationZhan, T., Rindtorff, N., & Boutros, M. (2017) · Oncogene · doi:10.1038/onc.2016.304 · Cited by 2,626
Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers
Vlachogiannis, G., Hedayat, S., Vatsiou, A., Jamin, Y., Fernández-Mateos, J., Khan, K., Lampis, A., Eason, K., Huntingford, I., Burke, R., et al. (2018) · Science · doi:10.1126/science.aao2774 · Cited by 2,096
Metadata
- Authors
- van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., McLaren-Douglas, A., Blokker, J., Jaksani, S., Bartfeld, S., Volckman, R., van Sluis, P., Li, V. S. W., Seepo, S., Sekhar Pedamallu, C., Cibulskis, K., Carter, S. L., McKenna, A., Lawrence, M. S., Lichtenstein, L., Stewart, C., Koster, J., Versteeg, R., van Oudenaarden, A., Saez-Rodriguez, J., Vries, R. G. J., Getz, G., Wessels, L., Stratton, M. R., McDermott, U., Meyerson, M., Garnett, M. J., & Clevers, H.
- Affiliations
- Wellcome Sanger Institute (GB)
- Broad Institute (US)
- The Netherlands Cancer Institute (NL)
- European Bioinformatics Institute (GB)
- Diakonessenhuis hospital (NL)
- Royal Netherlands Academy of Arts and Sciences (NL)
- National Institute for Medical Research (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Garnett, Mathew J.
- Clevers, Hans
- ORCID
- Francis, Joshua M.
- Iorio, Francesco
- Pronk, Apollo
- Taylor-Weiner, Amaro
- Kester, Lennart
- Bartfeld, Sina
- Li, Vivian S.W.
- Cibulskis, Kristian
- Carter, Scott L.
- McKenna, Aaron
- Lawrence, Michael S.
- Stewart, Chip
- Versteeg, Rogier
- Vries, Robert G.J.
- Getz, Gad
- Wessels, Lodewyk
- Stratton, Michael R.
- McDermott, Ultan
- Meyerson, Matthew
- Garnett, Mathew J.
- Clevers, Hans
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 161
- Issue
- 4
- Pages
- 933-945
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6428276
- OpenAlex
- W1741548448
- Cited by
- 2,408
- References
- 64
- Citations by year
- 2026: 196 · 2025: 233 · 2024: 232 · 2023: 220 · 2022: 267 · 2021: 343 · 2020: 260 · 2019: 181 · 2018: 173 · 2017: 154 · 2016: 108 · 2015: 39
- FWCI
- 69.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- Francis Crick Institute (10105)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- colorectal cancer, tumor organoids, organoid biobank, Lgr5+ stem cells, R-spondin, Wnt signaling, porcupine inhibitor, RNF43 mutation, APC mutation, drug screening, personalized treatment, molecular subtypes, gene expression profiling
- MeSH terms
- DNA-Binding Proteins, Drug Screening Assays, Antitumor, Humans, Organ Culture Techniques, Organoids, Colorectal Neoplasms, Oncogene Proteins, Biological Specimen Banks, Ubiquitin-Protein Ligases, Precision Medicine
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