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Organoid models of gastrointestinal cancers in basic and translational research

Nature Reviews Gastroenterology & Hepatology volume 17, pages 203–222 (2020)Cite this article

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Abstract

Cancer is a major public health problem worldwide. Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality. Historically, the mechanisms of tumour initiation and progression in the gastrointestinal tract have been studied using cancer cell lines in vitro and animal models. Traditional cell culture methods are associated with a strong selection of aberrant genomic variants that no longer reflect the original tumours in terms of their (metastatic) behaviour or response to therapy. Organoid technology has emerged as a powerful alternative method for culturing gastrointestinal tumours and the corresponding normal tissues in a manner that preserves their genetic, phenotypic and behavioural traits. Importantly, accumulating evidence suggests that organoid cultures have great value in predicting the outcome of therapy in individual patients. Herein, we review the current literature on organoid models of the most common gastrointestinal cancers, including colorectal cancer, gastric cancer, oesophageal cancer, liver cancer and pancreatic cancer, and their value in modelling tumour initiation, metastatic progression and therapy response. We also explore the limitations of current organoid models and discuss how they could be improved to maximally benefit basic and translational research in the future, especially in the fields of drug discovery and personalized medicine.

Key points

  • Gastrointestinal cancers account for one-third of the total global cancer incidence and mortality; therefore, it is essential to translate knowledge from basic research into health benefits by advancing therapeutics.

  • Preclinical cancer research has been heavily reliant on cell lines and animal models, but both fail to recapitulate the original human tumours.

  • Organoid technology has emerged as a powerful alternative method for culturing gastrointestinal tumours and their corresponding normal tissues in a manner that preserves their genetic, phenotypic and behavioural traits.

  • Organoid models have been used to model tumour initiation, metastatic progression and therapy response of the most common gastrointestinal cancers, including colorectal cancer and liver cancer.

  • Clinical applications of patient-derived organoids are promising, as accumulating evidence has revealed the potential of organoid models in drug discovery, modelling therapy response and personalized medicine.

  • Current organoid models have multiple limitations; therefore, more work is necessary to enable them to maximally benefit basic and translational research in gastrointestinal cancers.

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Fig. 1: A schematic depicting the establishment and applications of organoid cultures.
Fig. 2: A schematic of applications of patient-derived tumour organoids in translational research.
Fig. 3: A schematic summarizing current issues in developing organoid cultures and approaches to overcome these limitations.

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Acknowledgements

The authors thank C. H. Szeto for comments on the structure and content of the manuscript.

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Authors and Affiliations

  1. Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong

    Harry Cheuk Hay Lau & Jun Yu

  2. UMC Utrecht Cancer Center, Utrecht Platform for Organoid Technology, Utrecht University, Utrecht, Netherlands

    Onno Kranenburg

  3. Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Haipeng Xiao

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  1. Harry Cheuk Hay Lau
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H.C.H.L. researched data for the article, made a substantial contribution to discussion of content, designed the figures, and wrote the article. O.K. and H.X. made a substantial contribution to discussion of content, and reviewed/edited the manuscript before submission. J.Y. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and reviewed/edited the manuscript before submission.

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Correspondence to Jun Yu.

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Nature Reviews Gastroenterology & Hepatology thanks Y. Zavros, H. Tiriac, D. Stange and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Lau, H.C.H., Kranenburg, O., Xiao, H. et al. Organoid models of gastrointestinal cancers in basic and translational research. Nat Rev Gastroenterol Hepatol 17, 203–222 (2020). https://doi.org/10.1038/s41575-019-0255-2

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