TY - JOUR
T1 - Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models
AU - Prasetyanti, Pramudita R.
AU - van Hooff, Sander R.
AU - van Herwaarden, Tessa
AU - de Vries, Nathalie
AU - Kalloe, Kieshen
AU - Rodermond, Hans
AU - van Leersum, Ronald
AU - de Jong, Joan H.
AU - Franitza, Marek
AU - Nürnberg, Peter
AU - Todaro, Matilde
AU - Stassi, Giorgio
AU - Medema, Jan Paul
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055478420&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30151914
U2 - https://doi.org/10.1002/ijc.31767
DO - https://doi.org/10.1002/ijc.31767
M3 - Article
C2 - 30151914
SN - 0020-7136
VL - 144
SP - 366
EP - 371
JO - International journal of cancer. Journal international du cancer
JF - International journal of cancer. Journal international du cancer
IS - 2
ER -