4.5 Article

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

Journal

CANCER RESEARCH AND TREATMENT
Volume 49, Issue 4, Pages 915-926

Publisher

KOREAN CANCER ASSOCIATION
DOI: 10.4143/crt.2016.322

Keywords

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

Categories

Funding

  1. National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea [1520100]
  2. Korean Health Technology R&D Project, Ministry for Health & Welfare, Republic of Korea [HI14C1940]
  3. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2013R1A1A2013612]
  4. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
  5. Ministry of Health & Welfare, Republic of Korea [HI14C3418]
  6. National Research Foundation of Korea [2013R1A1A2013612] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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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.

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