Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models

Pramudita R Prasetyanti; Sander R van Hooff; Tessa van Herwaarden; Nathalie de Vries; Kieshen Kalloe; Hans Rodermond; Ronald van Leersum; Joan H de Jong; Marek Franitza; Peter Nürnberg; Matilde Todaro; Giorgio Stassi; Jan Paul Medema

doi:10.1002/ijc.31767

Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models

Int J Cancer. 2019 Jan 15;144(2):366-371. doi: 10.1002/ijc.31767. Epub 2018 Oct 22.

Authors

Pramudita R Prasetyanti^{1

2}, Sander R van Hooff^{1

2}, Tessa van Herwaarden^{1

2}, Nathalie de Vries^{1

2}, Kieshen Kalloe^{1

2}, Hans Rodermond^{1

2}, Ronald van Leersum^{1

2}, Joan H de Jong^{1

2}, Marek Franitza³, Peter Nürnberg³, Matilde Todaro⁴, Giorgio Stassi⁵, Jan Paul Medema^{1

2}

Affiliations

¹ Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM) and Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
² Oncode Institute, Academic Medical Center, Amsterdam, The Netherlands.
³ Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
⁴ DIBIMIS, University of Palermo, Palermo, Italy.
⁵ Cellular and Molecular Pathophysiology Laboratory, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy.

Abstract

Patient-derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach to CRC. Moreover, we showed that tumor cell proliferation was associated with successful PDX establishment and able to distinguish patient with poor clinical outcomes within CMS2 group.

Keywords: CMS; PDX; cell proliferation; colorectal cancer; tumor subtype; xenograft.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colorectal Neoplasms / pathology*
Disease Models, Animal*
Heterografts*
Humans
Mice
Xenograft Model Antitumor Assays / methods*