The Plasticity of Stem-Like States in Patient-Derived Tumor Xenografts

  • Alastair H. Davies
  • Fraser Johnson
  • Kirsi Ketola
  • Amina Zoubeidi
Part of the Molecular and Translational Medicine book series (MOLEMED)


Preclinical cancer models often fail to capture the complex heterogeneity of a patient’s tumor and as such lack clinical predictive power. In an attempt to circumvent this issue, patient-derived xenograft (PDX) models have been developed as powerful tools for translational research as they retain much of the intratumor heterogeneity present in the donor tumor. Such cellular heterogeneity is very important as it likely represents a major therapeutic hurdle. The existence of subpopulations of cells in tumors with heightened tumor-initiating capacity and self-renewal potential, often termed “cancer stem cells” (CSCs), has been postulated to play a principal role in treatment resistance. In this chapter, we discuss the contribution of cell-autonomous and cell-extrinsic factors in governing cell plasticity and the CSC state, along with how these processes are recapitulated in the PDX model. Limitations with regard to current generation PDX models are discussed along with strategies to improve several aspects of the model with respect to preserving cell plasticity and stem-like states.


PDX Cancer stem cells Heterogeneity Plasticity Epigenetics Tumor microenvironment 



Cancer-associated fibroblast


Cell-derived matrices


Cancer stem-like cell


Extracellular matrix


Epidermal growth factor


Focal adhesion kinase


Histone deacetylase inhibitors


Hypoxia inducible factors


Natural killer


Patient-derived xenograft


Phosphoinositide 3-kinase


Tumor microenvironment


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Alastair H. Davies
    • 1
    • 2
  • Fraser Johnson
    • 1
    • 2
  • Kirsi Ketola
    • 1
    • 2
  • Amina Zoubeidi
    • 1
    • 2
  1. 1.Vancouver Prostate CentreVancouverCanada
  2. 2.Department of Urologic Sciences, Faculty of MedicineUniversity of British ColumbiaVancouverCanada

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