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

International Journal of Cancer. Journal International Du Cancer
Pramudita R PrasetyantiJan Paul Medema

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.

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Citations

Sep 4, 2019·International Journal of Cancer. Journal International Du Cancer·Jiahao ShiXianqun Fan
Feb 27, 2020·Clinical and Experimental Medicine·Jun Xie, Yan Lin
Jun 4, 2020·Cancers·George M RamzyPatrycja Nowak-Sliwinska
Jun 18, 2020·Cancers·Javier Molina-CerrilloAlfredo Carrato
Apr 21, 2020·World Journal of Gastroenterology : WJG·Florian BürtinMichael Linnebacher
Sep 16, 2020·Cancer Metastasis Reviews·Michael W LeeAnna Capasso
Oct 3, 2020·Annals of Gastroenterological Surgery·Hiroshi SawayamaHideo Baba
Feb 1, 2019·Current Gastroenterology Reports·David G MenterScott Kopetz
Jun 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Giulia RizzoStefania Vetrano
Jun 7, 2021·Journal of Experimental & Clinical Cancer Research : CR·Erika DurinikovaSabrina Arena
Dec 5, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Jingjing ShiPek-Lan Khong

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Datasets Mentioned

BETA
GSE100480
GSE39582

Methods Mentioned

BETA
xenografts

Software Mentioned

GSA R package
GSEA
limma R package
Combat
db
sva
hgu133plus2
R package

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