Abstract 2206: Genomics of Drug Sensitivity in Cancer (GDSC): A resource for therapeutic biomarker discovery in cancer cells.

Abstract

Abstract The Genomic of Drug Sensitivity in Cancer (GDSC; www.cancerRxgene.org) resource facilitates development of targeted cancer therapies through pre-clinical identification of therapeutic biomarkers. GDSC is the largest public resource for information on drug sensitivity in cancer cells and links these data to extensive genomic information to identify molecular features that influence anticancer drug response. There is compelling evidence that alterations in cancer genomes strongly influence clinical responses to anticancer therapies. There are several examples where genomic changes are used as molecular biomarkers to stratify patients most likely to benefit from a treatment (e.g. BRAF in melanoma). Despite these successes, the majority of cancer drugs have not been linked to specific molecular features that could be used to direct their clinical use to maximize patient benefit. We are using pharmacogenomic profiling in cancer cell lines as a biomarker discovery platform by systematically linking pharmacological data with genomic information in cancer cells. The GDSC database contains drug sensitivity data generated from high-throughput screening performed by the Cancer Genome Project at the Wellcome Trust Sanger Institute and the Center for Molecular Therapeutics at Massachusetts General Hospital using a collection of >1,200 cancer cell lines. GDSC release v3 (November 2012) contains drug sensitivity data for almost 80,000 experiments, describing response to 142 anticancer drugs across over 700 cancer cell lines. To identify molecular markers of drug response, cell line drug sensitivity data are integrated with large genomic datasets obtained from COSMIC (Catalogue of Somatic Mutations in Cancer), including information on somatic mutations in cancer genes, gene amplification and deletion, tissue type and transcriptional data. Analysis of GDSC data is through a web portal based on queries of specific anticancer drugs or cancer genes. Interactive graphical representations of the data are used throughout with links to related resources, and all datasets are freely available and downloadable. The GDSC database will undergo significant expansion in coming years as drug sensitivity and genomic datasets increase in size and complexity. GDSC provides a unique public resource incorporating large drug sensitivity and genomic datasets to facilitate discovery of new therapeutic biomarkers for cancer therapies. Citation Format: Wanjuan Yang, Jorge Soares, Patricia Greninger, Elena Edelman, Howard Lightfoot, Simon Forbes, Ramaswamy Sridhar, P. Andrew Futreal, Daniel Haber, Michael Stratton, Cyril Benes, Ultan McDermott, Mathew Garnett. Genomics of Drug Sensitivity in Cancer (GDSC): A resource for therapeutic biomarker discovery in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2206. doi:10.1158/1538-7445.AM2013-2206