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  • Review Article
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Functional precision oncology using patient-derived assays: bridging genotype and phenotype

Nature Reviews Clinical Oncology volume 20, pages 305–317 (2023)Cite this article

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Abstract

Genomics-based precision medicine has revolutionized oncology but also has inherent limitations. Functional precision oncology is emerging as a complementary approach that aims to bridge the gap between genotype and phenotype by modelling individual tumours in vitro. These patient-derived ex vivo models largely preserve several tumour characteristics that are not captured by genomics approaches and enable the functional dissection of tumour vulnerabilities in a personalized manner. In this Review, we discuss several examples of personalized functional assays involving tumour organoids, spheroids and explants and their potential to predict treatment responses and drug-induced toxicities in individual patients. These developments have opened exciting new avenues for precision oncology, with the potential for successful clinical applications in contexts in which genomic data alone are not informative. To implement these assays into clinical practice, we outline four key barriers that need to be overcome: assay success rates, turnaround times, the need for standardized conditions and the definition of in vitro responders. Furthermore, we discuss novel technological advances such as microfluidics that might reduce sample requirements, assay times and labour intensity and thereby enable functional precision oncology to be implemented in routine clinical practice.

Key points

  • The use of personalized tumour models as patient avatars has the potential to individualize cancer care.

  • Different personalized tumour models have been established, including organoids, spheroids and explants. These models have key differences that need to be considered when designing a functional assay.

  • Early studies have identified important factors that impede clinical implementation; technological developments such as microfluidics technology might also help to overcome these hurdles.

  • Further prospective clinical trials will be needed to enable the clinical implementation of personalized functional assays.

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Fig. 1: From genotype to phenotype.
Fig. 2: Patient-derived ex vivo tumour models.

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Acknowledgements

Images for Fig. 2 were kindly provided by O. Kranenburg of Utrecht University, B. L. Emmink of Utrecht University and V. Veninga of Netherlands Cancer Institute.

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  1. Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Allard W. J. van Renterghem, Joris van de Haar & Emile E. Voest

  2. Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Allard W. J. van Renterghem, Joris van de Haar & Emile E. Voest

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van Renterghem, A.W.J., van de Haar, J. & Voest, E.E. Functional precision oncology using patient-derived assays: bridging genotype and phenotype. Nat Rev Clin Oncol 20, 305–317 (2023). https://doi.org/10.1038/s41571-023-00745-2

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