4.8 Review

Next-generation cancer organoids

Journal

NATURE MATERIALS
Volume 21, Issue 2, Pages 143-159

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41563-021-01057-5

Keywords

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Funding

  1. Stanford Bio-X Bowes Graduate Fellowship
  2. National Institutes of Health Training Grant in Biotechnology [T32-GM008412]
  3. Stanford Lieberman Fellowship
  4. National Institutes of Health [R01 EB027171, U01 DK085527]
  5. National Science Foundation [NSF CBET 2033302]
  6. Personalized Health and Related Technologies Initiative from the ETH Board
  7. Swiss 3R Competence Centre
  8. Ecole Polytechnique Federale de Lausanne (EPFL)

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The translation discusses how organotypic models of patient-specific tumors are changing our understanding of cancer heterogeneity and personalized medicine. These models can preserve genetic, proteomic, morphological, and pharmacotypic features of the parent tumor in vitro, and offer genomic and environmental manipulation. However, current cancer organoid culture techniques are uncontrolled and irreproducible, hindering the acceleration of insights into patient care.
Organotypic models of patient-specific tumours are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. These advancements are, in part, attributed to the ability of organoid models to stably preserve genetic, proteomic, morphological and pharmacotypic features of the parent tumour in vitro, while also offering unprecedented genomic and environmental manipulation. Despite recent innovations in organoid protocols, current techniques for cancer organoid culture are inherently uncontrolled and irreproducible, owing to several non-standardized facets including cancer tissue sources and subsequent processing, medium formulations, and animal-derived three-dimensional matrices. Given the potential for cancer organoids to accurately recapitulate the intra- and intertumoral biological heterogeneity associated with patient-specific cancers, eliminating the undesirable technical variability accompanying cancer organoid culture is necessary to establish reproducible platforms that accelerate translatable insights into patient care. Here we describe the current challenges and recent multidisciplinary advancements and opportunities for standardizing next-generation cancer organoid systems. This Review summarizes limitations in the current techniques used for patient-derived cancer organoid culture and highlights recent advancements and future opportunities for their standardization.

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