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Capturing colorectal cancer inter‐tumor heterogeneity in patient‐derived xenograft (PDX) models
Author(s) -
Prasetyanti Pramudita R.,
Hooff Sander R.,
Herwaarden Tessa,
Vries Nathalie,
Kalloe Kieshen,
Rodermond Hans,
Leersum Ronald,
Jong Joan H.,
Franitza Marek,
Nürnberg Peter,
Todaro Matilde,
Stassi Giorgio,
Medema Jan Paul
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31767
Subject(s) - colorectal cancer , medicine , cancer , tumor heterogeneity , oncology , cancer research , bioinformatics , biology
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.