Abstract 3172: Pooled RNAi screens in xenograft mouse models.

Abstract We present results of clonal analysis studies aimed at characterizing the heterogeneity of in vivo cancer cell growth in xenograft models. Using a high-throughput sequencing method, we followed the fate of thousands of individually bar-coded cancer cells grown in vitro, or in vivo upon sub-cutaneous implantation in immunocompromised mice. By precisely and reproducibly quantifying clonal cancer cell growth in vivo, we found that xenograft growth is marked by a phenomenon of clonal dominance, in which a small subset of cancer cell sub-clones account for the bulk of the resulting tumor mass. This phenomenon has important implications for the field of in vivo shRNA screening. Subsequently, we developed a new proprietary clonal RNAi screening platform specifically designed to circumscribe the clonal dominance effect in xenograft model viability screens. We used this technology to perform xenograft “drop-out” screens in a panel of tumorigenic cell lines, including human breast, ovarian and colon carcinomas. Preliminary data will be presented. These results demonstrate that complex pooled shRNA libraries provide a highly efficient, flexible, and unique tool for in vivo screens aimed the discovery of potential cancer therapy targets. Citation Format: Donato Tedesco, Kyle Bonneau, Mikhail Makhanov, Debbie Deng, Paul Diehl, Peiqing Sun, Alex Chenchik. Pooled RNAi screens in xenograft mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3172. doi:10.1158/1538-7445.AM2013-3172