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Generation of Prostate Cancer Patient-Derived Xenografts to Investigate Mechanisms of Novel Treatments and Treatment Resistance

  • Hung-Ming Lam
  • Holly M. Nguyen
  • Eva CoreyEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1786)

Abstract

Treatment advances lead to survival benefits of patients with advanced prostate cancer. These treatments are highly efficacious in a subset of patients; however, similarly to other cancers, after initial responses the tumors develop resistance (acquired resistance) and the patients succumb to the disease. Furthermore, there is a subset of patients who do not respond to the treatment at all (de novo resistance). Preclinical testing using patient-derived xenografts (PDXs) has led to successful drug development, and PDXs will continue to provide valuable resources to generate clinically relevant data with translational potential. PDXs demonstrate tumor heterogeneity observed in patients, preserve tumor-microenvironment architecture, and provide clinically relevant treatment responses. In view of the evolving biology of the advanced prostate cancer associated with new treatments, PDXs representing these new tumor phenotypes are urgently needed for the study of treatment responses and resistance. In this chapter, we describe methodologies used to establish prostate cancer PDXs and use of these PDXs to study de novo and acquired resistance.

Key words

Prostate cancer Abiraterone Enzalutamide Resistance Testosterone 

Notes

Acknowledgements

We would like to thank the Richard M. Lucas Foundation and the Prostate Cancer Foundation for their long-term support for the generation and characterization of prostate cancer PDX models. The work is also supported by NIH PO1 CA085859 (to Robert L. Vessella) and the PNW Prostate Cancer SPORE NIH P50 CA097186 (to Peter S. Nelson). We very much appreciate Dr. Robert Vessella and Dr. Paul H. Lange for their continuous support of our work. We extend our gratitude to the patients who donated their tissues for research and the assistance of the many clinicians who facilitated this process.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of UrologyUniversity of WashingtonSeattleUSA

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