Abstract

Abstract With the complete molecular characterization of the major cancer types in sight, it is clear that only a minority of the cancer genes represent readily accessible drug targets. Furthermore, mechanistic biomarkers that predict response to targeted therapies remain scant. To address these challenges, we employ large-scale chemical genetic screens in isogenic cells to systematically uncover gene-drug interactions. For instance, using a panel of engineered cell lines we have recently identified several known and novel breast cancer vulnerabilities and a mechanism of resistance to drugs inhibiting the PI3K/mTOR pathway. We have performed similar screens in an isogenic lung cancer model that attempts to capture some of the higher order gene-drug interactions. In addition, I will present our efforts concerning the generation of a collection of haploid human knockout cells covering the majority of expressed genes that represents a powerful platform empowering haploid genetics in human cells. Citation Format: Sebastian Nijman. Gene-drug interaction screens in cancer using isogenic cell models. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Synthetic Lethal Approaches to Cancer Vulnerabilities; May 17-20, 2013; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(5 Suppl):Abstract nr IA18.

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