Abstract LB-039: PDX and PDX-derived cell line development from peritoneal metastasis of micropapillary serous carcinoma of the ovary

Abstract

Abstract Peritoneal spread is an indicator of poor prognosis in patients with micropapillary serous carcinoma of the ovary. In general, these patients are treated by surgical cytoreduction followed by intraperitoneal chemotherapy. Although this strategy has encouraging efficacy, personalized treatment regimens may potentially further improve efficacy of cancer management. To investigate such a personalized approach, patient-derived xenografts (PDX) and PDX-derived cell lines from peritoneal implants from micropapillary serous carcinoma of the ovary are developed and characterized. Freshly resected peritoneal implants from consenting donors were obtained. A cell suspension was made and immediately subperitoneally implanted in female immunocompromised mice and expanded as peritoneal metastasis (PM)-PDX. A transplantable PM-PDX was established from 1/1 donor. Histology confirmed the micropapillary and cribriform growth pattern, which was further characterized by intraluminal tumor budding. PM-PDX dissociated cells were maintained as a plastic-adherent cell culture up to 20 passages. The PM-PDX derived cell line is characterized by an epithelial morphotype with doubling time of 42 hours and shows a colony formation efficiency of 25-40% independent of estrogen signaling. The cell line is sensitive to the microtubule stabilizing agent paclitaxel (IC50 = 1.485 nM) and the allosteric MEK inhibitor trametinib (IC50 = 1.299 nM). Future work will provide insights on the mutational status of RAS and RAF, important indicators of potential MEK-targeted personalized medicine. Citation Format: Elien De Thaye, An Vermeulen, Wim Ceelen, Jan Van Bocxlaer, Olivier De Wever. PDX and PDX-derived cell line development from peritoneal metastasis of micropapillary serous carcinoma of the ovary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-039.