Abstract 1210: A patient derived xenograft tumor model platform for “mouse trials”

Abstract

Abstract From Chinese cancer patients, close to 600 patient derived xenograft (PDX) tumor models have been established (> P3, three passages in mice) at GenenDesign through serial passages in the immune-compromised nude mice. The major collection of GenenDesign PDX tumor model platform represents cancer types that are prevalent in Asian patients, including gastric cancer (> 200 models), esophageal cancer (>100 models), liver cancer (∼50 models), pancreatic cancer (>60 models) and lung cancer (> 80 models). Establishment of variant PDX models from the same patient tumor is on-going to support translational studies of tumor heterogeneity. Initial characterization indicates that the mouse PDX models have captured the major histopathological characteristics of the original human tumors. Reproducible growth curves for PDX models (>P3) support their usage in efficacy analysis of anti-cancer therapeutic agents. Response curves to SoC (standard of care) chemotherapies such as Paclitaxel for lung cancer, FOLFOX for gastric cancer and Sorafenib for liver cancer have been established in the PDX tumor models, providing a baseline for further investigation of novel therapies in a combination setting. On-going molecular characterization including oncogene mutational analysis and target specific IHC and FISH analysis has identified panels of PDX tumor models with aberrations in key oncogenic signaling pathways, including lung panels with EGFR overexpression or KRAS mutations, gastric panels with FGFR2 amplification or being HER2 positive, lung and gastric panels with cMET overexpression. Testing of Herceptin in the gastric HER2 positive tumor panel resulted in observations similar to that from the ToGA trial. At the same time, Herceptin resistant PDX tumor variants (de novo or acquired) were identified or established. The PDX tumor model panels facilitate translational studies in a “mouse trial” format in a setting similar to clinical trials to test patient stratification strategies and drug response predictive biomarkers for emerging therapeutic modalities. Citation Format: Ying Yan, Tengfei Yu, Wei Du, Guosheng Tong, Yuefei Yang, Tingting Tan, Xuqin Yang, Zhenhua Liu, Jiali Gu, Liang Hua, Wei Zhang, Xin K. Ye, Zhenyu Gu. A patient derived xenograft tumor model platform for “mouse trials”. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1210. doi:10.1158/1538-7445.AM2014-1210