Abstract

Abstract Although molecular profiling of human tumors is now routine, the use of this data to guide therapy remains limited to a subset of patients. In particular, pediatric cancers often harbor a signature molecular alteration but few other mutations. 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 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. These studies now allow us to define a Cancer Dependency Map. Using these datasets and approaches, we have defined new categories of potential cancer targets, identify synthetic lethal candidates in pediatric and adult cancers and have developed a method to systematically identify molecular pleiotropy. These approaches promise to further operationalize precision cancer medicine. Citation Format: William C. Hahn. Using the cancer dependency map [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY27-03.

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