48
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development. Xenografts preserved the histopathology, genome architecture, and global gene expression of donor tumors. Moreover, their aggressiveness matched patient observations, and their response to androgen withdrawal correlated with tumor subtype. The panel includes the first xenografts generated from needle biopsy tissue obtained at diagnosis. This advance was exploited to generate independent xenografts from different sites of a primary site, enabling functional dissection of tumor heterogeneity. Prolonged exposure of adenocarcinoma xenografts to androgen withdrawal led to castration-resistant prostate cancer, including the first-in-field model of complete transdifferentiation into lethal neuroendocrine prostate cancer. Further analysis of this model supports the hypothesis that neuroendocrine prostate cancer can evolve directly from adenocarcinoma via an adaptive response and yielded a set of genes potentially involved in neuroendocrine transdifferentiation. We predict that these next-generation models will be transformative for advancing mechanistic understanding of disease progression, response to therapy, and personalized oncology.

          Related collections

          Author and article information

          Journal
          Cancer Res
          Cancer research
          American Association for Cancer Research (AACR)
          1538-7445
          0008-5472
          Feb 15 2014
          : 74
          : 4
          Affiliations
          [1 ] Authors' Affiliations: Vancouver Prostate Centre; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia; Departments of Experimental Therapeutics and Radiation Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada; Departments of Medicine and Pathology and Laboratory Medicine, Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York.
          Article
          0008-5472.CAN-13-2921-T
          10.1158/0008-5472.CAN-13-2921-T
          24356420
          3cba1343-6323-4351-a223-8e2a2a4c9a70
          ©2013 AACR.
          History

          Comments

          Comment on this article