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Medium-Throughput Drug- and Radiotherapy Screening Assay using Patient-Derived Organoids.

Authors
  • Putker, Marrit1
  • Millen, Rosemary2
  • Overmeer, René3
  • Driehuis, Else4
  • Zandvliet, Maurice M J M5
  • Clevers, Hans2
  • Boj, Sylvia F3
  • Li, Qi-Xiang6
  • 1 Crown Bioscience Netherlands B.V. , (Netherlands)
  • 2 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht. , (Netherlands)
  • 3 Hubrecht Organoid Technology (HUB).
  • 4 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht; Pathology dept, University Medical Center Utrecht. , (Netherlands)
  • 5 Department of Clinical Sciences - Companion Animals, Faculty of Veterinary Medicine, Utrecht University.
  • 6 Crown Bioscience Inc.; [email protected]
Type
Published Article
Journal
Journal of Visualized Experiments
Publisher
MyJoVE Corporation
Publication Date
Apr 30, 2021
Issue
170
Identifiers
DOI: 10.3791/62495
PMID: 33999032
Source
Medline
Language
English
License
Unknown

Abstract

Patient-derived organoid (PDO) models allow for long-term expansion and maintenance of primary epithelial cells grown in three dimensions and a near-native state. When derived from resected or biopsied tumor tissue, organoids closely recapitulate in vivo tumor morphology and can be used to study therapy response in vitro. Biobanks of tumor organoids reflect the vast variety of clinical tumors and patients and therefore hold great promise for preclinical and clinical applications. This paper presents a method for medium-throughput drug screening using head and neck squamous cell carcinoma and colorectal adenocarcinoma organoids. This approach can easily be adopted for use with any tissue-derived organoid model, both normal and diseased. Methods are described for in vitro exposure of organoids to chemo- and radiotherapy (either as single-treatment modality or in combination). Cell survival after 5 days of drug exposure is assessed by measuring adenosine triphosphate (ATP) levels. Drug sensitivity is measured by the half-maximal inhibitory concentration (IC50), area under the curve (AUC), and growth rate (GR) metrics. These parameters can provide insight into whether an organoid culture is deemed sensitive or resistant to a particular treatment.

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