Abstract 327: Establishment of patient primary ovarian cancer xenograft models for test of anticancer agents.

Abstract BACKGROUND Human xenograft tumor models established by transplantation of human tumor cell lines into immunodifficient mice have been routinely used for preclinical test of anticancer agents. But tumor cell lines have a relatively low transplantability, which resulted in a limited number of tumor models available for selection of right tumor modes for test of targeted therapeutics. Recently, we have developed a large number of patient primary ovarian tumor xenograft models by transplanting human fresh ovarian tumor tissues into nude mice, which have been employed for preclinical test of clinically used drugs and novel anticancer agents for their chemosensitivity screening. METHODS The fresh ovarian tumor samples were collected from local hospitals. The tumor fragments of 2-3 mm were subcutaneously implanted in the flanks of nude mice by trocar needle. Sixteen tumor fragments were grafted into four mice from one patient tumor tissue (passage 0). The clinically used drugs included cisplatin, carboplatin, paclitaxel, and docetaxel. The histology and gene sequence of the established primary tumor models were analyzed and compared with patients’ original tumors. RESULTS A total of 77 patients’ ovarian tumor samples were implanted into nude mice; and 38 primary tumor models have been established with a tumor taking rates of 49% for the first passage. The tumor taking rates were higher in the later passages ranged from approximately 85-100%. The therapeutic efficacy of the test anticancer drugs was consistent with their clinical findings. The patients’ primary ovarian tumor xenografts from all 5 passages retained a similarity in architecture, histopathological morphology, and genomic mutation status to their patients’ original tumors. CONCLUSIONS The patient primary tumor model system can provide a larger number of models for selection of right models for preclinical testing novel agents based on their anticancer mechanism. The primary tumor models retain a similarity in histology and genomic mutation status to their patients’ original tumors. They may predict more relevant clinical response rate and higher correlation with clinical findings than use of traditional xenograft models established from long-term cultured cancer cell lines. Especially, they have advantages for test of target-oriented therapeutics in new drugs development programs. Citation Format: Changnian Liu, Chunping Xu, Wenwei Li, Wen Zhou, Yong Liu, Rui Zhou, Ning Zhang. Establishment of patient primary ovarian cancer xenograft models for test of anticancer agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 327. doi:10.1158/1538-7445.AM2013-327

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