Abstract IA17: Defining cancer dependency maps

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 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 CRISPR-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. In recent studies, we have expanded these efforts to patient-derived organoids and cell lines, which will expand the number and types of cancers represented and allow for the interrogation of other cancer phenotypes. These studies allow us to define a global cancer dependencies map, which will help further operationalize precision cancer medicine. Citation Format: William C. Hahn. Defining cancer dependency maps [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA17.