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

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

Affiliations
  • 1Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
  • 2Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. garden.lee@samsung.com
  • 3Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
  • 4Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 5Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
  • 6Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
  • 7Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
  • 8Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

Keyword

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

MeSH Terms

Animals
Biology
Cell Line
Drug Therapy, Combination
Eosine Yellowish-(YS)
Epidermal Growth Factor
Erlotinib Hydrochloride
Female
Hematoxylin
Heterografts*
Humans
Mice
Microsatellite Repeats
Molecular Targeted Therapy
Ovarian Neoplasms*
Precision Medicine
Translational Medical Research
Tumor Burden
Eosine Yellowish-(YS)
Epidermal Growth Factor
Erlotinib Hydrochloride
Hematoxylin
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