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

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

Abstract

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.

Keywords

PDX Cancer stem cells Heterogeneity Plasticity Epigenetics Tumor microenvironment 

Abbreviations

CAF

Cancer-associated fibroblast

CDMs

Cell-derived matrices

CSC

Cancer stem-like cell

ECM

Extracellular matrix

EGF

Epidermal growth factor

FAK

Focal adhesion kinase

HDACis

Histone deacetylase inhibitors

HIFs

Hypoxia inducible factors

NK

Natural killer

PDX

Patient-derived xenograft

PI3K

Phosphoinositide 3-kinase

TME

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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