Abstract PL08-04: High-throughput drug screens in cancer cell models to enable precision cancer medicine

Abstract

Abstract Alterations in cancer genomes strongly influence clinical responses to therapy and can be used as molecular biomarkers of response to targeted agents. However, the identification of biomarkers for effective patient stratification remains a considerable challenge for the development of effective therapies. We are performing large-scale drug sensitivity screens using genetically characterised in vitro cellular models of human cancer. Cancer cells are profiled for differential sensitivity to clinical, pre-clinical and experimental anti-cancer compounds and drug response is linked with genomic features. We aim to identify the molecular features of cancer cells which impact on drug sensitivity and resistance, and investigate the molecular rationale for the observed sensitivity. This provides insights into mechanism of drug action, identifies opportunities for re-purposing existing drugs for new indications, and enables the identification of biomarkers to facilitate the development of targeted cancer therapies. I will describe results from our recent analysis of how cancer-driving alterations identified from the analysis of 11,000 patient tumours correlate with response to 265 compounds profiled in a panel of 1,000 human cancer cell-lines. This comprehensive analysis provides an initial glimpse of the landscape of pharmacogenomic interactions operative in human cancer, and is a resource to identify novel therapeutic possibilities for selected cancer sub-populations. Citation Format: Mathew Garnett. High-throughput drug screens in cancer cell models to enable precision cancer medicine. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr PL08-04.