Abstract 3247: Primary tumor cell lines generated from patient-derived-xenograft models are useful tools for study tumor biology, drug efficacy

Patient-derived-xenograft (PDX) models have been widely used in the biomedical research. They recapitulate the genomic diversity/heterogeneity of patient tumors, maintain a lot of the characteristics of the original tumors and showed much better correlation with clinical outcome comparing to traditional cell line derived xenograft models. However, the relatively low throughput and time-consuming nature of PDX studies prevent them from being used in large scale screening or mechanistic studies. To address this, different cancer cell lines have been developed in our laboratory from the PDX tumors. We performed STR analyses to validate their identity. Whole exome sequencing, RNA-seq, SNP array 6.0 were performed on selected cell lines. When we compared 5 of these cell lines with their parental PDX tumors, over 93% of the CNVs identified in the cell lines were also found in the corresponding PDX models. Copy number analyses also revealed similar focal amplifications both on the cell lines and the original PDX models. More importantly, efficacy studies using different compounds showed similar drug responses using in vitro cell culture, xenografts using these cell lines and original PDX models. Our data demonstrated the high fidelity of these cell lines to their parental PDX models. In addition, we generated cell lines from progressed tumors upon exposure to long term drug treatment. The pair of treatment sensitive and resistant tumor cell lines facilitated the research on development of drug resistance. Overall, while maintaining the genetic background and phenotypic characteristics of the PDX models, these primary tumor cell lines serve as a bridge between the high-throughput drug screening and highly clinical relevant PDX models. They represent useful tools in biomedical research. Citation Format: Gang Hu, Yong Huang, Fubo Xie, Xuzhen Tang, Xueyan Yang, Kunyan Liu, Yixin Zhang, Weikang Tao, He Zhou. Primary tumor cell lines generated from patient-derived-xenograft models are useful tools for study tumor biology, drug efficacy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3247. doi:10.1158/1538-7445.AM2015-3247