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

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

Author information

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

KEYWORDS:

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

PMID:
28052650
PMCID:
PMC5654149
DOI:
10.4143/crt.2016.322
[Indexed for MEDLINE]
Free PMC Article

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