Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases
Open accessAbstract
Significance: Chemotherapy has been proven in clinical studies to improve overall survival significantly. Unfortunately, there is a significant degree of heterogeneity in tumor chemosensitivity, often resulting in unnecessary treatment and needless exposure to toxic side-effects. A platform is needed that can identify preemptively which patients will or will not benefit from treatment. Tumor organoids, 3D cultures of cancer cells, present such an individualized platform. In this study we demonstrate that organoid cultures can be established from metastatic biopsy specimens with a high success rate and genetically represent the metastasis they were derived from. These data support the translation of this innovative technology to the clinic as an ex vivo screening platform for tailoring treatment.
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Checkpoint inhibitors and other immuno-oncology drugs can be screened in tumor organoid models that include immune cells.
“Checkpoint inhibitors and other immuno-oncology (IO) drugs can also be screened in tumor organoid models that include immune cells157.”
From Organoids (2022) · cites this paper as [157]
The Significance and Discussion sections describe patient-derived tumor organoids as a potential ex vivo platform for screening treatments. They do not describe organoid models containing immune cells or screening checkpoint inhibitors or other immuno-oncology drugs. (LLM, conf=0.85)
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- Authors
- Weeber, F., van de Wetering, M., Hoogstraat, M., Dijkstra, K. K., Krijgsman, O., Kuilman, T., Gadellaa-van Hooijdonk, C. G. M., van der Velden, D. L., Peeper, D. S., Cuppen, E. P. J. G., Vries, R. G., Clevers, H., & Voest, E. E.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands;
- Department of Radiotherapy, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands;
- Department of Molecular Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands;
- Royal Netherlands Academy of Arts and Sciences (NL)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-10-12
- Volume
- 112
- Issue
- 43
- Pages
- 13308-13311
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4629330
- OpenAlex
- W2198641185
- Cited by
- 482
- References
- 16
- Citations by year
- 2026: 31 · 2025: 31 · 2024: 52 · 2023: 45 · 2022: 58 · 2021: 85 · 2020: 65 · 2019: 47 · 2018: 34 · 2017: 23 · 2016: 11
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Barcode for Life Foundation (-)
- Center for Personalized Cancer Treatment (-)
- NWO Zwaartekracht (-)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- patient-derived tumor organoids, metastatic colorectal cancer, tumor biopsy, genetic diversity, somatic mutations, copy number profiles, driver genes, precision oncology, ex vivo drug testing
- MeSH terms
- Base Sequence, Humans, Molecular Sequence Data, Neoplasm Metastasis, Organoids, Genetic Variation, Colorectal Neoplasms, Sequence Analysis, DNA, Cell Culture Techniques, Antineoplastic Protocols, Genes, Neoplasm, Precision Medicine
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