Abstract 1483: Targeting oncogenic enhancer activity with a small-molecule CBP/P300 bromodomain inhibitor

Abstract

Abstract Transcriptional networks are often dramatically altered in cancer, this dysregulation occurring at both the genetic and epigenetic level. Recently much attention has been given to the role of enhancer-driven gene expression in cancer, with the observation that numerous key oncogenes are driven by super-enhancers. This opens up the possibility for therapeutic intervention with small molecules that modulate enhancer activity, leading to control of expression of otherwise un-drugable oncogenes. CBP/P300 are histone acetyl transferases (HATS) that are critical mediators of enhancer activity. Here we use a novel small molecule inhibitor of the CBP/P300 bromodomain to specifically probe the role of these HATS at enhancers, and more broadly evaluate the consequences of enhancer disruption on cancer cell growth in vitro and in vivo. Citation Format: Ryan Raisner, Russell Bainer, Emily Chan, Jesse Garcia, Mark Merchant, Karen Gascoigne. Targeting oncogenic enhancer activity with a small-molecule CBP/P300 bromodomain inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1483.