BETter together: exploiting BRD4-functions in transcription to inform rational combinations

The identification of inhibitors of the BET family of bromodomain proteins (BETi) has fueled our knowledge about functions of their targets, the transcriptional regulators BRD2/3/4 and T, and this class of antitumor agents holds promise in clinical development [1]. However, even in pre-clinical models derived from hematological malignancies, which are in general more sensitive to BETi than those originating from solid cancers [2], use of BETi as single agents rarely results in strong apoptosis induction or tumor regressions at tolerated doses [1], underscoring the requirement for rational combination approaches