Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies

Cancer Res Treat. 2017 Oct;49(4):915-926. doi: 10.4143/crt.2016.322. Epub 2017 Jan 4.

Abstract

Purpose: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.

Materials and methods: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.

Results: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).

Conclusion: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

Keywords: Molecular targeted therapy; Ovarian epithelial cancer; Patient-derived xenograft model; Precision medicine; Subrenal capsule implantation.

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Biopsy
  • Carboplatin / pharmacology
  • Carcinoma, Ovarian Epithelial
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Genomic Instability
  • Heterografts
  • Humans
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / pharmacology
  • Translational Research, Biomedical
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carboplatin
  • ErbB Receptors
  • Paclitaxel