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

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Patient-Derived Xenograft Models of Human Cancer

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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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.

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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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Authors and Affiliations

  1. Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada

    Alastair H. Davies, Fraser Johnson, Kirsi Ketola & Amina Zoubeidi Ph.D.

  2. Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Alastair H. Davies, Fraser Johnson, Kirsi Ketola & Amina Zoubeidi Ph.D.

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  1. Alastair H. Davies
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  2. Fraser Johnson
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  4. Amina Zoubeidi Ph.D.
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Correspondence to Amina Zoubeidi Ph.D. .

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  1. Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Yuzhuo Wang

  2. Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, British Columbia, Canada

    Dong Lin

  3. Living Tumor Laboratory, BC Cancer Agency/Vancouver Prostate Centre, Vancouver, British Columbia, Canada

    Peter W. Gout

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Davies, A.H., Johnson, F., Ketola, K., Zoubeidi, A. (2017). The Plasticity of Stem-Like States in Patient-Derived Tumor Xenografts. In: Wang, Y., Lin, D., Gout, P. (eds) Patient-Derived Xenograft Models of Human Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55825-7_6

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