Abstract 5455: Integrative analysis of the Cancer Cell Line Encyclopedia reveals genetic and transcriptional predictors of compound sensitivity

Abstract

Abstract Comprehensive genomic characterization of cancer is proceeding at a rapidly accelerating pace, mainly due to the expanded use of massively parallel sequencing. Despite the promise of cancer genomics, many cancer drugs still fail in the clinic due to nonresponsive patients and this translates into a significant unmet medical need. Accurate predictions of which patients are more likely to respond to drugs in development could speed clinical trials and personalize treatments. Here we propose the use of a compendium of experimentally tractable cancer model systems, ∼1000 human genomically-annotated cancer cell lines (at the level of gene expression, DNA copy number alterations and mutations), coupled with pharmacological profiling, to systematically link genetic and transcriptional features to drug response. This resource, the Cancer Cell Line Encyclopedia (CCLE), is available online at www.broadinstitute.org/ccle. Through computational predictive modeling we have both rediscovered molecular features that predict response to several drugs and also uncovered a number of novel potential biomarkers of sensitivity and resistance to targeted agents and chemotherapy drugs. For instance, we have found that response to topoisomerase 1 inhibitors seem to be driven by expression of a single gene. We have also observed that tissue lineage is a key predictor for sensitivity to certain compounds, providing rationale for clinical trials of these drugs in particular cancer types. Our cell line-based platform provides a valuable tool for the development of personalized cancer medicine, revealing critical tumor dependencies and helping to stratify patients for clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5455. doi:10.1158/1538-7445.AM2011-5455