Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both <i>in vitro</i> and <i>in vivo</i> BRD4 inhibition also decreased the expression of <i>NOTCH3</i> targets, including <i>HES1</i> Chromatin immunoprecipitation revealed that BRD4 was present at the <i>NOTCH3</i> promoter.Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.
Suppression of BRD4 using small-molecule BET inhibitors JQ1 and I-BET151, or dual kinase-bromodomain inhibitor volasertib, led to robust and broad antitumor effects across all subclasses of ovarian cancer.