Abstract 2715: Establishment of patient primary colorectal tumor xenograft models for test of anticancer agents.

Abstract

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 right models to test novel anticancer agents. Recently, we have developed a large number of patients’ primary colorectal tumor xenograft models by transplanting human fresh colorectal tumor tissues into nude mice, which have been employed for preclinical test of standard care of drugs and novel anticancer agents for their chemosensitivity screening. METHODS The fresh colorectal 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 standard care of drugs as controls included 5-FU, irinotecan, oxaliplatin, Erbitux, and Avastin. The histopathology and gene sequencing of the established primary tumor models were analyzed and compared with patients’ original tumors. RESULTS A total of 180 patients’ colorectal tumor samples were implanted into nude mice; and 93 patient tumor derived models have been established with a tumor taking rates of 52% for the first passage. The tumor taking rates were higher in the later passages ranged from approximately 80-100%. The therapeutic efficacy of the test drugs was consistent with their clinical findings. The patients’ primary colorectal tumor xenografts from 5 passages retained a similarity in architecture, histopathological morphology, and genomic mutation status to the patients’ original tumors. CONCLUSIONS The patient primary tumor model system can provide a larger number of models for selection of right models to test novel agents in preclinical setting based on their anticancer mechanism. The primary tumor models retain a similarity in histology and genomic mutation status to their counterpart patients’ original tumors and may predict more relevant clinical response 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: Ning Zhang, Chunping Xu, Wen Wei Li, Wen Zhou, Yong Liu, Fang He, Rui Zhou, Changnian Liu. Establishment of patient primary colorectal tumor 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 2715. doi:10.1158/1538-7445.AM2013-2715