The recent advances in in vitro 3D culture technologies, such as organoids, have opened new avenues for the development of novel, more physiological human cancer models. Such preclinical models are essential for more efficient translation of basic cancer research into novel treatment regimens for patients with cancer. Wild-type organoids can be grown from embryonic and adult stem cells and display self-organizing capacities, phenocopying essential aspects of the organs they are derived from. Genetic modification of organoids allows disease modelling in a setting that approaches the physiological environment. Additionally, organoids can be grown with high efficiency from patient-derived healthy and tumour tissues, potentially enabling patient-specific drug testing and the development of individualized treatment regimens. In this Review, we evaluate tumour organoid protocols and how they can be utilized as an alternative model for cancer research.
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The authors thank K. Kretzschmar and J. Meijerink for critical reading of the manuscript. We are grateful for support from the Dutch Cancer Society (KWF) and the Alpe d’HuZes Bas Mulder Award to J.D. (KWF/Alpe d’HuZes, 10218) and for the support of Oncode Institute to H.C.
J.D. and H.C. are named as inventors on several patents related to leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ stem cell-based organoid technology.
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The number and appearance of chromosomes in the nucleus of a cell.
- Feeder cells
A layer of cells that is used to support the growth of a cell culture (that is, stem cell cultures) by secretion of important growth factors into the culture medium.
A mouse-derived ex vivo basement membrane substitute that is used to support 3D growth of organoid cultures.
- Intraepithelial lymphocytes
(IELs). Lymphocytes residing in the epithelial layer of mammalian mucosal linings, such as the small and large intestines, lungs, upper respiratory tract, reproductive tract and skin.
- Mutation signatures
Unique combinations of mutation types caused by different mutational processes.
- Base excision repair
A DNA repair mechanism that removes damaged bases (oxidized, alkylated or deaminated) that could otherwise cause mutations.
A pouch located between the small and large intestine that is considered to be the beginning of the large intestine and is thus part of the gastrointestinal tract.
A process of programmed cell death initiated by loss of cell–matrix interactions in anchorage-dependent cells.
- Serrated colon adenomas
A precursor colorectal cancer (CRC) subtype that is characterized by a serrated histopathological morphology. Serrated CRCs are genetically distinct from the classical adenocarcinomas. Whereas classical adenocarcinomas are typically initiated by mutations in the WNT pathway (for example, adenomatous polyposis coli (APC)), serrated CRCs are likely initiated by BRAF mutations.
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Drost, J., Clevers, H. Organoids in cancer research. Nat Rev Cancer 18, 407–418 (2018). https://doi.org/10.1038/s41568-018-0007-6
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