Abstract
Abstract To complement ongoing large-scale characterization of cancer genomes, we have developed genome-scale tools to systematically annotate the function of genes involved in cancer initiation and progression. In particular, we have dissected the signaling pathways related to one of the most frequently mutated oncogenes KRAS. Using both gain-of-function (ORFs) and loss-of-function (RNAi and CRISPR-Cas9) approaches, we have identified new components of KRAS effector pathways that are essential for the survival of KRAS driven cancers. We have also performed comprehensive genetic screens to identify genes that modulate the response of KRAS-driven cancer cell lines to clinical-grade MEK inhibitors. Together these ongoing approaches provide new insights into KRAS signaling and identify potential targets for KRAS-driven cancers. Citation Format: William C. Hahn. Systematic interrogation of KRAS in cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA28.
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