BET inhibitors as potential anticancer agents

In human cancers, epigenetic alterations such as DNA methylation and histone modifications can play a key role in the dysregulation of gene expression leading to the silencing of tumor suppressor genes or to the overexpression of proto-oncogenes. The bromodomain (BRD) is the sole protein domain capable of recognizing the epsilon-N-acetylation of lysine histone residues, thus mediating epigenetic regulation of DNA transcription. Increasing preclinical evidence shows the BRD might be an interesting potential therapeutic target in human cancer. In particular, selective inhibitors of the bromodomain and extraterminal (BET) family are currently under clinical evaluation in early clinical trials. In this review, we discuss the function of the BRD proteins (and of the BET family proteins in particular) in cellular regulation and in carcinogenesis, and review the preclinical and early clinical evidence suggesting a putative role for BET inhibitors as a new class of anticancer drugs.