Abstract 2783: Variability of HER2 expression between in vitro and in vivo models within gastric cancer cell lines

Abstract In the process of developing individualized cancer therapeutics, tumor derived cell line based preclinical (in vitro and in vivo) methods have been widely used. Patient derived genome analysis revealed significant cancer biomarkers for targeted drug development. Classic cancer biomarker, HER2, overexpression was discovered as a cancer biomarker and as a druggable target in breast cancer, which lead to the development of Trastuzumab. HER2 is overexpressed in 10-25% of gastric cancer, and treatment with Trastuzumab showed positive yet limited activity in advanced gastric cancer treatment in the ToGA study. These results present HER2 as an attractive target for gastric cancer. However, Gillet and colleagues reported the challenges in the use of in vitro and in vivo studies for drug validation and development. They reported variance in gene expression patterns between the in vitro and in vivo context within a single cancer cell line. In our study using gastric cancer derived cell lines, we observed differences in HER2 expression between in vitro and in vivo xenograft model. Also, we show the potential promising in vivo xenograft model in the development of HER2 targeting agents for gastric cancer. Eleven out of 25 gastric cancer cell lines showed HER2 expression, which was demonstrated using the IHC assay on a cell microarray. Sixteen out of 25 cell lines successfully produced xenograft models. Gastric cancer cell lines (SNU-5, SNU-16, SNU-638, SNU-1967, MKN-1, MKN-28, and NUGC-3) that had no HER2 expression when cultured in vitro showed HER2 expression in vivo. Two cell lines (NCC-19 and NCI-N87) that had HER2 expression in vitro showed a decrease in HER2 expression in vivo. Three cell lines (SNU-484, SNU-668, and SNU-719) showed various levels of increase in HER2 expression. Two cell lines showed minor to no changes in HER2 expression. NUGC-4 had consistent significant HER2 expression levels in both assays, while MKN-45 had consistent insignificant to no HER2 expression. Our study demonstrates inconsistency in HER2 gene expression between in vitro and in vivo cancer cell line models for the first time in gastric cancer. Citation Format: Youme Gim, Hee Seo Park, Hae Rim Jung, Hae Ryung Chang, Seungyoon Nam, Yong Doo Choi, Ja-Lok Ku, Yon Hui Kim. Variability of HER2 expression between in vitro and in vivo models within gastric cancer cell lines. [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 2783. doi:10.1158/1538-7445.AM2014-2783