Abstract 2414: In vitro profiling of gastric and liver cancer cell lines developed from Asian cancer patients

Abstract

Abstract In East Asia stomach and liver cancer are the 2nd and 3rd most common malignancies and there is a high medical need to develop new drugs. However, well characterized in vitro and in vivo models developed from Asian cancer patients are rare. The Oncotest tumor xenograft and cell line repository used for profiling of anticancer compounds comprised mainly models established from patients with a Caucasian origin. Now the Oncotest tumor repository was extended by 8 gastric and 12 liver cancer cell lines of Asian origin obtained from KCLB (Korean Cell Line Bank) and JCRB (Japanese Collection of Research Bioresources). Additionally, 2 head & neck cancer cell lines from KCLB and the gastric cell line GXA 3011L established at Oncotest from a Korean patient-derived tumor xenograft were added to the panel. Among these 23 cell lines, 6 currently grow subcutaneously as solid tumor xenografts in nude mice. Gene expression profiles (Affymetrix chip HG-U133 plus 2.0 consisting of 38,500 genes) have been determined for all cell lines and respective xenografts. Doubling times as determined for all cell lines were in the range of 23 h (MKN45) to 76 h (SNU-423). In vitro chemosensitivity to standard of care (e.g. 5-FU, doxorubicin, oxaliplatin, paclitaxel) and selected targeted drugs (everolimus, lapatinib) was assessed by a fluorescence based monolayer cytotoxicity assay as well as by the ex-vivo clonogenic assay. The drugs showed diverse patterns of selectivity and potency in both assays. As an example, the mTor inhibitor everolimus exhibited pronounced activity with IC50 values in the low nanomolar range towards the liver cancer cell lines SNU-398, SNU-475, SNU-878 and SNU-886 in the monolayer as well as in the clonogenic assay. In contrast, towards gastric cancer cell lines no or only marginal activity was detected for everolimus in the monolayer assay. The HER2 / EGFR kinase selective inhibitor lapatinib showed selective activity towards the gastric cancer cell line NUGC-4 (IC50=0.16µM), the liver cancer cell line JHH-4 (IC50=0.56µM) and the H&N cancer cell line SNU-1076 (IC50=0.54µM). Overall, in vitro activity profiles for 12 SOC drugs and correlations with molecular alterations, target expression and pathway activation will be presented. This collection of cell lines is of high relevance for the development of drugs against the most widely occurring cancers in East Asia, by providing models for the study of the biology and response to novel anticancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2414. doi:10.1158/1538-7445.AM2011-2414