Abstract 2777: Advantages of patient primary tumor models versus tumor cell lines derived models for testing anticancer therapeutics.

Abstract

Abstract BACKGROUND While the tumor xenograft models derived from human cancer cell lines in immunodeficient mice have been widely used for testing cytotoxic anticancer agents, new drug development has moved from cytotoxic agents to molecular target-directed therapeutics. Consequently, there is a need to identify tumor types and individual patient tumors that express the target that will benefit tumor model selection and be more indicative for clinical trials. Therefore, the tumor models used in preclinical development should be “disease-oriented” and target-directed. Recently, we have developed a large number of patient primary tumor xenograft models by transplanting patients’ fresh tumor tissues into immunodeficient mice, which have been used for testing novel therapeutics. METHODS The fresh tumor samples were collected from local hospitals. The tumor fragments of 1-2 mm were subcutaneously implanted in the flanks of nude mice. The histopathology and genomic mutation status of primary tumor xenografts were analyzed and compared with patients’ original tumors. The tested clinically used drugs included cisplatin, carboplatin, paclitaxel, docetaxel, irinotecan, doxorubicin, 5-FU, gemcitabine, gefitinib, erlotinib, pemetrexed, Erbitux, and Avastin. RESULTS A total of 1,120 patients’ primary tumor tissues have been implanted into immunodeficient mice and 348 patient tumor-derived models have been established. The tumor taking rates of the different tumor types in the first passage were colorectal (52%), ovarian (49%), esophageal (67%), small cell lung cancer (89%), non-small cell lung cancer (45%), gastric (27%), kidney (17%), glioblastoma (21%), breast (11%), liver (12%), pancreatic (50%), lymphoma (33%), and leukemia (23%). The tumor taking rates were higher in the later passages for the various tumor types, ranged from approximately 80-100%. The clinically used drugs produced tumor inhibition rates ranged from 20-90%, which were consistent with their clinical findings. The patient primary tumor xenografts presented a similar histopathological morphology and the same genomic mutation status to their counterparts of the patients’ original tumors. CONCLUSIONS The results suggest that patient primary tumor-derived xenograft model system can provide a larger number of models within the same tumor histological type for models selection based on antitumor mechanism of test agents. They also provide a unique renewable source of tumor material for target identification and biomarker evaluation. The preclinical results obtained from primary tumor models may give a better predictive value than the traditional human tumor xenograft models established by inoculation of in vitro cultured cancer cell lines. Especially, they have advantages for testing target-oriented therapeutics in new drugs development programs. Citation Format: Changnian Liu, Wenwei Li, Wen Zhou, Rong Liu, Rui Zhou, Fang He, Chunping Xu, Chang Bai. Advantages of patient primary tumor models versus tumor cell lines derived models for testing anticancer therapeutics. [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 2777. doi:10.1158/1538-7445.AM2013-2777