A patient-derived explant (PDE) model of hormone-dependent cancer

Mol Oncol. 2018 Sep;12(9):1608-1622. doi: 10.1002/1878-0261.12354. Epub 2018 Aug 16.

Abstract

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.

Keywords: ex vivo culture; patient-derived explant; preclinical tumor model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Epithelial Cells
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gelatin Sponge, Absorbable
  • Heterografts
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Organoids
  • Patient-Specific Modeling*
  • Precision Medicine / methods*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Translational Medical Research
  • Tumor Cells, Cultured
  • Tumor Microenvironment

Substances

  • AR protein, human
  • Estrogen Receptor alpha
  • Ki-67 Antigen
  • MKI67 protein, human
  • Receptors, Androgen