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

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)366-371
JournalInternational journal of cancer. Journal international du cancer
Volume144
Issue number2
Early online date2018
DOIs
Publication statusPublished - 2019

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