Abstract IA14: Understanding the complex biology of KRAS mutant cancers using genetic screens

Apart from identifying synthetic lethal genes, genetic screens have the potential to reveal much about the basic biology of cell lines. We utilize two techniques, one analytical and one experimental, to demonstrate how genetic screens can also reveal which pathways are on in cell lines and what are the phenotypic consequences of pathway perturbation. First, we apply a clustering analysis of genome-scale CRISPR screening data to map out active pathways in cancer cell lines and to discover novel members of signaling transduction pathways and protein complexes. Secondly, we performed a combinatorial siRNA screen that knocks out multiple genes at once and measures five functional parameters to comprehensively describe the effects of pathway inhibition. Application of these two techniques to KRAS mutant cancer cell lines reveals a trove of biological information that highlights the vast heterogeneity of this disease and subtype-specific opportunities for therapeutic intervention.Citation Format: Tina L. Understanding the complex biology of KRAS mutant cancers using genetic screens [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA14.

Source: Molecular Cancer Therapeutics - October 2, 2017 Category: Cancer & Oncology Authors: L, T. Tags: New Technology and Bioinformatics: Oral Presentations - Invited Abstracts Source Type: research