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First-Generation Tumor Xenografts: A Link Between Patient-Derived Xenograft Models and Clinical Disease

  • Xin Dong
  • Peter W. Gout
  • Lu Yi
  • Yinhuai Wang
  • Yong Xu
  • Kuo Yang
Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

First-generation tumor xenografts, also called primary xenografts, are patient-derived tumor xenografts (PDXs) in the initial human-to-mouse generation harboring tumor tissues directly derived from patients. Compared to transplantable PDX models established via serial passaging, the first-generation xenografts are advantageous in several aspects, such as shorter engraftment time and better retention of intra-tumoral heterogeneity and tumor microenvironment of the original patients’ tumor tissues. Although first-generation xenografts have not been widely used or well characterized, an increasing amount of evidence suggests that they provide valuable tools for fulfilling real-time personalized drug testing, improving predictive powers of in vivo preclinical models in anticancer drug discovery and development, and studying cancer-stromal interactions in the context of an intact human cancer tissue microenvironment. In this chapter, we review the current comprehension of first-generation xenografts and their potential applications in contemporary preclinical cancer research and management of the disease.

Keywords

First-generation xenografts PDX Precision medicine Tumor heterogeneity Tumor microenvironment Cancer-associated stroma Drug development 

Abbreviations

ECM

Extracellular matrix

NSCLC

Non-small cell lung cancer

PCa

Prostate cancer

PDX

Patient-derived xenograft

S.C.

Subcutaneous

SRC

Subrenal capsule

Notes

Acknowledgments

We thank Drs. Dong Lin and Hui Xue at the Living Tumor Laboratory (www.livingtumorlab.com) for their original inputs and suggestions. This study was supported by Dr. Yuzhuo Wang’s grants from the Canadian Institutes of Health Research, Terry Fox Research Institute, BC Cancer Foundation, Prostate Cancer Canada, and Princess Margaret Hold’em for Life.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Xin Dong
    • 1
  • Peter W. Gout
    • 1
    • 2
  • Lu Yi
    • 3
  • Yinhuai Wang
    • 3
  • Yong Xu
    • 4
  • Kuo Yang
    • 4
  1. 1.Living Tumor Laboratory, BC Cancer Agency/Vancouver Prostate CentreVancouverCanada
  2. 2.Department of Experimental Therapeutics, BC Cancer Research CentreVancouverCanada
  3. 3.Department of UrologyThe Second Xiangya Hospital, Zhongnan UniversityChangshaChina
  4. 4.Tianjin Institute of UrologyTianjin Medical UniversityTianjinChina

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