Carvedilol (Carv) has been shown to enhance the antiproliferative activity of the rexinoid Bexarotene (Bex). This study focuses on BRD4, an epigenetic reader, to study the mechanisms behind the synergy of Bex+Carv. ChIP-seq analysis suggested genomic enrichment of BRD4 at enhancer sequences controlling genes that promote cell proliferation and metastasis. BRD4 suppression reduced cell proliferation and the antiproliferative effect of Bex+Carv was found to be independent of BRD4. However, BRD4 regulates cell morphology and modulates the expression of the tumor suppressors PTEN and DUSP5.