Abstract 5264: Advantages of patient primary tumor models versus tumor cell lines established models for testing anticancer agents

Abstract

Abstract BACKGROUND While the tumor xenograft models established by inoculation of human cancer cell lines into immunodeficient mice have been widely used for testing novel cytotoxic anticancer agents, new drug development has moved from general cytotoxic agents to molecular target-directed therapeutics. Consequently, there is a need to identify tumor types and individual patient tumors that express the target and could benefit from more selective therapies in clinical trials. Therefore, the in vivo models used in preclinical development should be “disease-oriented” and target-directed. Recently, we have developed patients’ primary tumor xenograft models by transplanting patients’ fresh tumor fragments into nude mice, which have been used for preclinical test of anticancer agents. METHODS The fresh tumor samples were collected from local hospitals. The tumor fragments of 1-2 mm were subcutaneously implanted in the flanks of the nude mice. The histopathology and genomic mutation status of primary tumor xenografts were analyzed and compared with patients’ original tumors. The clinically used drugs included cisplatin, paclitaxel, docetaxel, irinotecan, doxorubicin, 5-FU, gemcitabine, gefitinib, and erlotinib, avastin. RESULTS A total of 748 patients’ primary tumor samples have been implanted into nude mice, 256 patient tumor-derived models have been established. The tumor taking rates of the different tumor types in the first passage were colorectal (60%), ovarian (47%), esophageal (63%), small cell lung cancer (100%), non-small cell lung cancer (50%), gastric (28%), kidney (12%), glioblastoma (19%), breast (7%), liver (10%), and acute lymphocytic leukemia (25%). The tumor taking rates were higher in the later passages for the various tumor types, ranged from approximately 70-100%. The clinically used anticancer drugs produced tumor inhibition rates ranged from 20-90%, which were consistent with their clinical findings. The patient primary tumor xenografts from all five generations presented a similar histopathological morphology and the same genomic mutation status as their counterparts of the patients’ original tumors. CONCLUSIONS These 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 cancer cell lines. Especially, they have advantages for testing target-oriented therapeutics in new drugs discovery and development programs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5264. doi:1538-7445.AM2012-5264