Xenograft and organoid model systems in cancer research

Abstract

Patient-derived tumour xenografts and tumour organoids have become important preclinical model systems for cancer research. Both models maintain key features from their parental tumours, such as genetic and phenotypic heterogeneity, which allows them to be used for a wide spectrum of applications. In contrast to patient-derived xenografts, organoids can be established and expanded with high efficiency from primary patient material. On the other hand, xenografts retain tumour-stroma interactions, which are known to contribute to tumorigenesis. In this review, we discuss recent advances in patient-derived tumour xenograft and tumour organoid model systems and compare their promises and challenges as preclinical models in cancer research.

Keywords: cancer; organoids; preclinical models; tumour heterogeneity; xenografts.

Figure 1. Timeline PDTX and PDTO development

(Toolan, 1953; Taetle et al, 1987; Fu et al, 1992; Beckhove et al, 2003; Fichtner et al, 2004; Shultz et al, 2005; Wang et al, 2005; Cutz et al, 2006; Sato et al, 2009, 2011; Hennessey et al, 2011; Gao et al, 2014; Karthaus et al, 2014; Boj et al, 2015; Lee et al, 2018; Li et al, 2018, 2019; Sachs et al, 2018; Yan et al, 2018; Kopper et al, 2019; Schutgens et al, 2019).

Figure 2. Schematic representation of patient‐derived tumour xenografts and organoids

PDTXs preserve tumour heterogeneity and tumour–stroma interactions. PDTOs grow in a provided basement membrane extract and can be established from epithelial cancer cells as well as normal epithelial tissue. Both models allow for several translational applications that contribute to development of therapeutic cancer treatments. Part of this figure was adapted from Sachs and Clevers (2014).

Figure 3. Pie chart with the different cancer types that can be grown as PDTX (left) and PDTO (right) marked in green

In general, the engraftment efficiency of PDTXs is lower than the success rate of PDTO establishment.