title: Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Heo
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
authors.forename: William Chi
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Hong
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Jeon
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
authors.forename: Doo-Yi
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Yoo-Young
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Tae-Joong
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001706:Biopsy; D016190:Carboplatin / Q000494:pharmacology; D000077216:Carcinoma, Ovarian Epithelial; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D042822:Genomic Instability; D064593:Heterografts; D006801:Humans; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D057170:Translational Research, Biomedical; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: Molecular targeted therapy; Ovarian epithelial cancer; Patient-derived xenograft model; Precision medicine; Subrenal capsule implantation