Abstract IA1: Cancer dependencies defined by genomic alterations and targeted by small molecules
Stuart L. Schreiber · Cancer Research · 2012
Abstract The ability to sequence cancer genomes coupled with advances in small-molecule science provides a new foundation for creating safe and effective cancer therapeutics – ones delivered to patients based on the specific genomic alterations present in their cancer. Several examples now exist of small-molecule cancer drugs targeting protein kinases encoded by both wild-type and oncogenic alleles, and yielding high clinical response rates in patients with specific genetic features. However, these drugs target only a narrow range of proteins, benefit 1,600 genes, global assessment of DNA copy number, and global gene expression analysis. These characterizations are also available freely via an interactive web portal (broadinstitute.org/ccle). The compounds included in the Informer Set are known to have selective interactions with their target, and collectively target many distinct nodes in cancer cell circuitry, including but not limited to pathways modulating apoptosis, oxidative stress, chromatin signaling, mitotic stress, hypoxic stress, proteotoxic stress, and metabolism. Using robust analytical methods including cell-line and compound filtering, we correlated the sensitivity measurements with genomic alterations in cancer cell lines to identify dependencies conferred by specific genotypes. I will describe the current content of the Resource and provide multiple illustrations of its use, including the use of additional analytical tools not included in the Resource but readily and freely accessible elsewhere. Citation Format: Stuart L. Schreiber. Cancer dependencies defined by genomic alterations and targeted by small molecules [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA1.