Abstract 2831: Collateral lethality: A new target for personalized oncology

Large-scale genomic profiling efforts, such as The Cancer Genome Atlas (TCGA) have painted an unprecedentedly detailed picture of the genetic alterations that underlie carcinogenesis, yet the key challenge remains as to how to turn this information into actionable therapies. Genomic deletions are a frequent event in diverse cancers, which inactivate a limited number of tumor suppressor genes (“driver”-events) but frequently include many chromosomal neighbors as “passengers”, some of which play critical but redundant roles in normal cellular housekeeping. The overall hypothesis we propose to test is that collateral deletions of such “passenger” genes can be utilized as novel targets of synthetic lethality, an idea which we term “collateral lethality." The large number of passenger deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities …