title: Drug Sensitivity Assays of Human Cancer Organoid Cultures.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK.
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Francies
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barthorpe
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: McLaren-Douglas
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: Barendt
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK. mg12@sanger.ac.uk.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Garnett
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D009924:Organ Culture Techniques / Q000379:methods*; D009940:Organoids / Q000187:drug effects / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Cancer models; Cell lines; Drug screening; Drugs; Organoids; Preclinical; Targeted therapy