Abstract 612: Identification of selective inhibitors of diffuse-type gastric cancer cells by screening of annotated compounds

Abstract

Abstract Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and a poor prognosis. We have reported an E-cadherin/p53 double conditional knockout (DCKO) mouse line as the first genetically engineered one, which morphologically and molecularly recapitulates human DGC. We have also established mouse gastric cancer (GC) cell lines from DGC of the DCKO mice, demonstrating strong resistance to cytotoxic anti-cancer agents and high tumorigenic property when subcutaneously injected to nude mice. Then, we performed a synthetic lethal screening of 1535 annotated chemical compounds, and identified 27 candidates with selective inhibitory activity against the GC cell lines. These candidate drugs were classified into some classes, and members of the most potent class specifically attenuated cell proliferation of the GC cell lines by induction of apoptosis as well as suppressing tumor growth in vivo. Expectedly, E-cadherin-mutant and -low human gastric cancer cell lines were more sensitive to them in contrast to E-cadherin-intact ones. These findings may lead to development of novel drugs and discovery of potential targets in human DGC. Citation Format: Shu Shimada, Yoshimitsu Akiyama, Hiroshi Fukamachi, Yasuhito Yuasa, Shinji Tanaka. Identification of selective inhibitors of diffuse-type gastric cancer cells by screening of annotated compounds. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 612.