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Drug Sensitivity Assays of Human Cancer Organoid Cultures
Drug sensitivity testing utilizing preclinical disease models such as cancer cell lines is an important and widely used tool for drug development. Importantly, when combined with molecular data such as gene copy number variation or somatic coding mutations, associations between drug sensitivity and molecular data can be used to develop markers to guide patient therapies. The use of organoids as a preclinical cancer model has become possible following recent work demonstrating that organoid cultures can be derived from patient tumors with a high rate of success. A genetic analysis of colon cancer organoids found that these models encompassed the majority of the somatic variants present within the tumor from which it was derived, and capture much of the genetic diversity of colon cancer observed in patients. Importantly, the systematic sensitivity testing of organoid cultures to anticancer drugs identified clinical gene–drug interactions, suggestive of their potential as preclinical models for testing anticancer drug sensitivity. In this chapter, we describe how to perform medium/high-throughput drug sensitivity screens using 3D organoid cell cultures.
Keywords:Drug screening Organoids Cancer Cell lines Cancer models Drugs Targeted therapy Preclinical
We would like to thank the Wellcome Trust Sanger Institute cell line drug screening team for their help in developing these protocols and Stacey Price for critical reading of this manuscript. This work was funded with Awards from the Wellcome Trust (102696), Stand Up To Cancer (SU2C-AACR-DT1213), The Dutch Cancer Society (H1/2014-6919), and Cancer Research UK (C44943/A22536).
<Emphasis Type="Bold">Open Access</Emphasis> This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.