Cancer Research | 2019
Abstract 1653: Application of high-density tiling CRISPR screen technology to identify chromatin remodeler complex targets for drug discovery
Abstract
The mammalian SWI/SNF (mSWI/SNF or BAF) complexes are widely mutated in different human pathologies, presenting new therapeutic opportunities in a range of genetically well-defined cancers, including lung, endometrial, malignant rhabdoid tumor, synovial sarcoma, and others. In each of these settings, disruption of different SWI/SNF subunits have been shown to contribute to the tumorigenic potential via distinct mechanisms. This observation suggests the potential for a range of therapeutic targeting strategies to effectively inhibit cancer cell proliferation. Using high-density tiling sgRNA CRISPR/Cas9 screens, we have developed large-scale efforts to systematically identify critical protein functional domains within chromatin remodeling complex components to inform drug discovery strategies across several different cancer indications. Using this approach, we have successfully identified and validated critical functional domains in mSWI/SNF complex components with promising drug target potential in indications such as BRG1-mutated non-small cell lung adenocarcinoma and synovial sarcoma. Citation Format: Luis Soares, Michael Bocker, Qianhe Zhou, Cigall Kadoch, Ho Man Chan. Application of high-density tiling CRISPR screen technology to identify chromatin remodeler complex targets for drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1653.