Abstract SY42-03: Systematic interrogation of cancer dependencies and synthetic lethal interactions

Abstract

Abstract Although molecular profiling of human tumors is becoming increasingly routine, the use of this data to guide remains limited to a subset of patients. To complement genome characterization studies, we have used genome scale gain and loss of function approaches to identify genes required for cell survival and transformation. Specifically, we have performed systematic studies to interrogate rare alleles found altered in cancer genomes and used advances in synthetic gene synthesis to prospectively interrogate all possible alleles of known cancer genes. In parallel, we have performed both genome scale RNAi and CRISRP-Cas9 screens in hundreds of cancer cell lines to identify differentially essential genes and the context that specifies gene dependency. Integrating these studies with genome characterization of human tumors and protein-protein interaction databases facilitates the identification of genes and pathways required for the survival of specific cancer subtypes. These studies allow us to define a global cancer dependencies map, which will help further operationalize precision cancer medicine. Citation Format: William C. Hahn. Systematic interrogation of cancer dependencies and synthetic lethal interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY42-03.