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  • Review Article
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Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges

Nature Reviews Drug Discovery (2025)Cite this article

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Abstract

Organoids are 3D structures derived from stem cells that recapitulate key architectural and functional aspects of the corresponding tissue. Compared with conventional 2D cell lines, human organoids provide experimental models that more closely reflect human physiology. Their ability to capture the complexity and heterogeneity of human tissues enables the study of disease mechanisms, drug efficacy and toxicity. When generated from patient material, organoids also allow the assessment of individual drug responses. In this Review, we explore the utility of organoids in drug discovery. We outline current methodologies for generating and maintaining organoids, examine their applications in disease modelling, drug screening and safety evaluation, and consider regulatory aspects and the challenges for their broader adoption in drug discovery.

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Fig. 1: Pluripotent stem cell- and tissue stem cell-derived human organoids.
Fig. 2: Different types of organoid in disease modelling.
Fig. 3: Advanced organoid systems in disease modelling and drug safety evaluation.
Fig. 4: Strategies for automated high-throughput drug screening.

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Acknowledgements

The authors thank S. Fowler and A. Schneider from Roche Pharma Research and Early Development (pRED) for their thorough review and insightful suggestions. This work was supported by Oncode Accelerator, a Dutch National Growth Fund project under the grant number NGFOP2201; the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (grant number 024.003.001) funded by the Ministry of Education, Culture and Science of the government of the Netherlands; and the Oncode Institute (partly financed by the Dutch Cancer Society).

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Authors and Affiliations

  1. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Utrecht, The Netherlands

    Daisong Wang & Hans Clevers

  2. Oncode Institute, Utrecht, The Netherlands

    Daisong Wang & Hans Clevers

  3. Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Remi Villenave & Nadine Stokar-Regenscheit

  4. Institute of Human Biology (IHB), Roche Pharma Research and Early Development (pRED), Roche Innovation Center, Basel, Switzerland

    Hans Clevers

  5. The Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Hans Clevers

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D.W., R.V., and N.S.-R. researched data for article. All authors provided substantial contribution to discussion of content, wrote and reviewed and edited the article before submission.

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Correspondence to Hans Clevers.

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H.C. was the head of Pharma Research and Early Development (pRED) at Roche, Basel, and holds several patents related to organoid technology. His full disclosure can be found at: www.uu.nl/staff/JCClevers/Additional functions. R.V. and N.S.-R. are employees and stockholders of F. Hoffmann-La Roche Ldt.

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Wang, D., Villenave, R., Stokar-Regenscheit, N. et al. Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges. Nat Rev Drug Discov (2025). https://doi.org/10.1038/s41573-025-01317-y

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