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Review
. 2021 Sep 10;2(9):1011-1026.
doi: 10.1016/j.medj.2021.08.005.

Promises and Challenges of Organoid-Guided Precision Medicine

Shree Bose  1 , Hans Clevers  2   3 , Xiling Shen  1
Affiliations
Review

Promises and Challenges of Organoid-Guided Precision Medicine

Shree Bose et al. Med. .

Abstract

Organoids are self-organizing, expanding 3D cultures derived from stem cells. Using tissue derived from patients, these miniaturized models recapitulate various aspects of patient physiology and disease phenotypes including genetic profiles and drug sensitivities. As such, patient-derived organoid (PDO) platforms provide an unprecedented opportunity for improving preclinical drug discovery, clinical trial validation, and ultimately patient care. This article reviews the evolution and scope of organoid technology, highlights recent encouraging results using PDOs as potential patient "avatars" to predict drug response and outcomes, and discusses critical parameters for widespread clinical adoption. These include improvements in assay speed, reproducibility, standardization, and automation which are necessary to realize the translational potential of PDOs as clinical tools. The multiple entry points where PDOs may contribute valuable insights in drug discovery and lessen the risks associated with clinical trials are also discussed.

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Conflict of interest statement

Declaration of Interests S.B. declares no competing interests. X.S. is a co-founder and the CEO of Xilis Inc. H.C. is a member of the board of directors of Roche and a co-founder of Xilis Inc. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/.

Figures

Figure 1:
Figure 1:. Organoids derived from healthy and diseased tissue can be used to model various aspects of human physiology.
These include (clockwise from top left) modelling mutational cascades involved in carcinogenesis, features of pathogenic viral and bacterial infections, capturing the heterogeneity of tumor genetic subtypes, and cell-cell interactions that promote malignant cellular characteristics.
Figure 2:
Figure 2:. Using organoids can have impacts at multiple stages of the drug development pipeline, including during drug candidate screening, target validation, and clinical trials.
As the current paradigm results in only a few drugs introduced to market, patient derived organoids (PDOs) can reflect a greater range of patient backgrounds, thus identifying therapeutics which may be effective but had been rejected in prior models.
Figure 3:
Figure 3:
Retrospective studies have been used to establish the validity of PDO-guided therapies in clinic.
See this image and copyright information in PMC

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