Patient-Derived Organoids for Drug Development and Patient Stratification

Key to the development of the HUB Organoid Technology was the discovery of LGR5+ intestinal adult stem cells by the Clevers’ lab. With the identification of these stem cells, we were able to develop a culture system that allowed for the virtually unlimited, genetically and phenotypically stable expansion of the epithelial cells from animals including humans, both from healthy and diseased tissue (Sato et al., Nature 2009, 2011; Gastroenterology 2011; Huch et al., Nature 2013, Cell 2015; Boj et al., Cell 2015). Since the initial development, we have generated adult stem cell (ASC)-derived organoid models of different tissue origin like colon, lung, breast, pancreas and ovary for the study of Cancer, Cystic Fibrosis and other diseases (Dekkers, Nat Med 2013; van de Wetering, Cell 2015; Drost et al Nature 2015). These organoids have been characterized at the genetic and transcriptional level and provide an unique in vitro system for screening the efficacy of both approved drugs and compounds in preclinical development. Furthermore, ASC-derived organoids can serve as a patient avatar in clinical development and/or diagnostics. More recently, we were able to demonstrate that the in vitro response of ASC-derived organoids directly correlates with the clinical outcome of the patient from which the organoid was derived (Dekkers et al., Sci Trans Med 2016; Sachs et al., Cell 2018).

Learning Objectives:

1. Why HUB Organoids™ are considered to be superior 3D preclinical model systems

2. How to apply HUB Organoids to drug discovery

3. Impact and possibilities of HUB Organoids in (oncology and immuno-oncology) drug discovery