The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses
Open accessPublished version of a preprint
Abstract
In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived tumor organoids (PDTO) show enormous potential for preclinical testing; however, cultured tumor cells lose important characteristics, including the consensus molecular subtypes (CMS). To better reflect the cellular heterogeneity, we established the colorectal cancer organoid–stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that xenotransplantation or coculture with CAFs improves the transcriptomic fidelity and instructs subtype-specific stromal gene expression. Furthermore, functional profiling in coculture exposed CMS4-specific therapeutic resistance to gefitinib and SN-38 and prognostic expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as a common target. Our results demonstrate that colorectal cancer phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for a faithful representation of molecular subtypes and therapy responses ex vivo. Significance: Systematic characterization of the organoid–stroma biobank provides a resource for context dependency in colorectal cancer. We demonstrate a colorectal cancer subtype memory of PDTOs that is independent of specific driver mutations. Our data underscore the importance of functional profiling in cocultures for improved preclinical testing and identification of stromal resistance mechanisms. This article is featured in Selected Articles from This Issue, p. 2109
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A very recent study reported that coculture with CAFs promotes an increased resistance to SN-38 (irinotecan active metabolite) and gefitinib of CMS4 compared with CMS2 patient-derived tumor organoids (53).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [53]
In the citing paper
“studies based on coculture experiments have unambiguously demonstrated that CAFs reinforce the CMS4 traits of cancer cells (53).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
GSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440
Hallmarks of Cancer: New Dimensions
Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
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 Ensembl Variant Effect Predictor
McLaren, W., Gil, L., Hunt, S. E., Riat, H. S., Ritchie, G. R. S., Thormann, A., Flicek, P., & Cunningham, F. (2016) · Genome Biology · doi:10.1186/s13059-016-0974-4 · Cited by 8,099
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
Van der Auwera, G. A., Carneiro, M. O., Hartl, C., Poplin, R., del Angel, G., Levy‐Moonshine, A., Jordan, T., Shakir, K., Roazen, D., Thibault, J., et al. (2013) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1110s43 · Cited by 6,687
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,965
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · cited 1×
“Principal component analysis (PCA) showed distinct clustering and gene set enrichment analysis (GSEA) showed upregulation of inflammation and contractility signatures in CAFs as well as cell growth and translation signatures in normal fibroblasts, indicating that classic CAF features (27) are maintained in vitro.”
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–120 of 120
Zhang, P., Kobayashi, T., Nasu, M., Hashiguchi, T., Abe, M., Yamashita, K., Nomura, M., Orita, H., Fukunaga, T., Hashimoto, T., et al. (2026) · Journal of Visualized Experiments · doi:10.3791/69548
HMGCR loss is synthetic lethal with PIK3CD inhibition in colorectal cancer cells
Huang, J.-H., & Ma, J.-Q. (2026) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v18.i4.114220
Organoids as Next-Generation Models of Tumor Drug Resistance
Wang, L., Tang, Q., Zhong, L., He, M., Zhu, X., Zheng, Q., Long, L., Wang, Y., Jiang, Q., Wang, H., et al. (2026) · Cancer Biome and Targeted Therapy · doi:10.66505/cbtt.v1i1.9
Savadipour, A., Tummala, K. S., Muise, E. S., Buchanan, M., Vidimar, V., Veling, M. T., Liu, J., Kopinja, J. E., Schneider, C., Chan, B. P. H., et al. (2026) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2026.102549
Kryeziu, K., Klokkerud, S. M. K., Totland, M. Z., Moosavi, S. H., Reims, H. M., Bergsland, C. H., Eilertsen, I. A., Smeby, J., Lassen, K., Lundesgaard, K., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102840 · Cited by 3
Ni, X., Wang, C., Zhang, K., Zhang, M., Guo, J., Fan, W., Zheng, L., Jiang, T., & Zhang, G. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158360
Steup, C., Dosch, J., Dietz‐Fricke, C., Khosraviseftejani, S., Engel, E., Valk, A. F. D., Menger, D., Welker, P., Wild, P. J., Kennel, K. B., et al. (2026) · The Journal of Pathology · doi:10.1002/path.70082
Self-citationLi, P., Jin, N., Zhang, N., Yu, C., Lingling, E., Song, W., & (38117), L. Z. (2026) · iScience · doi:10.1016/j.isci.2026.116235
Current Practices and Considerations for Benchmarking Human Gastrointestinal Organoids
Brown, M. E., Gleizes, A. R., Yu, Q., Adhikari, U. D., Nagarajan, R., Rout, P., Camp, J. G., Yilmaz, Ö. H., Tape, C. J., Tyska, M. J., et al. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101832
Recent advancements and limitations of intestinal organoids for clinical applications
Khan, M. Z. I., Roy, S., Nair, S., Pinkey, A. A. H., Al-Hilal, T. A., Law, H. K., & Roy, S. (2026) · Progress in Biomedical Engineering · doi:10.1088/2516-1091/ae8107
Lupo, B., Catalano, I., & Trusolino, L. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02747-x
Zhang, K., Du, L., Sun, M., Lu, Y., Pang, M., Jiang, S., Liu, X., Dong, J., Jin, B., Xu, F., et al. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02751-1
Colorectal cancer organoid co-culture systems and their applications in drug screening
徐永强, Xing, T., Zhang, S., Zheng, S., Liu, C., Li, X., & Jia, J. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112277
Li, Y., Yang, Y., Zhao, L., Bian, Z., & Zhang, Z. (2026) · Bioengineering · doi:10.3390/bioengineering13080947
Clinical Translation of Patient‐Derived Organoids: Perspectives for Personalized Therapy in Cancer
Yue, H., Carchidi, D., Schmucker, P., Seiler, R. D., Kiss, B. M., Macedo‐Silva, C., & Julio, M. K. (2026) · International Journal of Cancer · doi:10.1002/ijc.70717
Finding a place for new approach methodologies (NAMs) in biomedical research
Schaffert, A., Ahluwalia, A. D., Bajramovic, J. J., Franco, N. H., Neuhaus, W., Olsson, I. A. S., & Sandvig, I. (2026) · Lab Animal · doi:10.1038/s41684-026-01806-6
Wang, X., Wang, Q., Wang, J., Ding, G., Huang, Y., Feng, Y., & Zou, B. (2026) · Materials Today Advances · doi:10.1016/j.mtadv.2026.100976
Tang, M., Shaoyi, L., Liang, Q., & Long, D. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1901112
Subtype or state? Rethinking the apCAF paradox and fibroblast plasticity in gastrointestinal cancers
Yu, Z., Hu, D., & An, Z. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.2000409
The preCDD Network as a Model for Academic Preclinical Cancer Drug Development in Germany
Ullrich, E., Weisel, K., Hölzel, M., Diegisser, T., Krones, D., Hudecek, M., Knapp, S., & Reinhardt, H. C. (2026) · Human Gene Therapy · doi:10.1177/10430342261502532
Self-citation
Metadata
- Authors
- Farin, H. F., Mosa, M. H., Ndreshkjana, B., Grebbin, B. M., Ritter, B., Menche, C., Kennel, K. B., Ziegler, P. K., Szabó, L., Bollrath, J., Rieder, D., Michels, B. E., Kress, A., Bozlar, M., Darvishi, T., Stier, S., Kur, I.-M., Bankov, K., Kesselring, R., Fichtner-Feigl, S., Brüne, B., Goetze, T. O., Al-Batran, S.-E., Brandts, C. H., Bechstein, W. O., Wild, P. J., Weigert, A., Müller, S., Knapp, S., Trajanoski, Z., & Greten, F. R.
- Affiliations
- Goethe University Frankfurt (DE)
- Georg Speyer Haus (DE)
- Innsbruck Medical University (AT)
- University of Freiburg (DE)
- 8Department of General and Visceral Surgery, University of Freiburg, Freiburg, Germany.
- Institute of Clinical Cancer Research (DE)
- 9Institute of Clinical Cancer Research IKF, Frankfurt am Main, Germany.
- Corresponding author
- Farin, Henner F.
- Greten, Florian R.
- ORCID
- Farin, Henner F.
- Mosa, Mohammed H.
- Ndreshkjana, Benardina
- Grebbin, Britta M.
- Ritter, Birgit
- Menche, Constantin
- Kennel, Kilian B.
- Ziegler, Paul K.
- Szabó, Lili
- Bollrath, Julia
- Rieder, Dietmar
- Michels, Birgitta E.
- Kress, Alena
- Bozlar, Müge
- Darvishi, Tahmineh
- Stier, Sara
- Kur, Ivan-Maximilano
- Bankov, Katrin
- Kesselring, Rebecca
- Fichtner-Feigl, Stefan
- Brüne, Bernhard
- Goetze, Thorsten O.
- Al-Batran, Salah-Eddin
- Brandts, Christian H.
- Bechstein, Wolf O.
- Wild, Peter J.
- Weigert, Andreas
- Müller, Susanne
- Knapp, Stefan
- Trajanoski, Zlatko
- Greten, Florian R.
- Venue
- Cancer Discovery
- Published
- 2023-07-25
- Volume
- 13
- Issue
- 10
- Pages
- 2192-2211
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC10551667
- OpenAlex
- W4385230305
- Cited by
- 120
- References
- 69
- Citations by year
- 2026: 39 · 2025: 44 · 2024: 31 · 2023: 6
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Discovery (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- LOEWE Center Frankfurt Cancer Institute (III L 5 - 519/03/03.001 - (0015))
- Deutsche Forschungsgemeinschaft (FOR2438 - FA1334/2-2)
- HORIZON EUROPE European Research Council (Advanced Grant PLASTICAN-101021078)
- Innovative Medicines Initiative 2 (EUbOPEN grant n°, 875510)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- colorectal cancer, patient-derived tumor organoids, cancer-associated fibroblasts, consensus molecular subtypes, tumor microenvironment, gefitinib resistance, MET, xenotransplantation, co-culture, preclinical drug testing
- MeSH terms
- Cancer-Associated Fibroblasts, Humans, Organoids, Tumor Cells, Cultured, Colorectal Neoplasms, Biological Specimen Banks, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
