Targeting BET Bromodomains in Cancer

Abstract

Cancer is frequently dependent on aberrant gene expression programs that might be vulnerable to targeting with novel therapeutics. Bromodomain and extraterminal domain (BET) proteins are powerful transcriptional coregulators often found as part of oncogenic transcriptional programs. The bromodomain functionality of BET proteins is highly druggable, and several product candidates are in clinical testing. While initial clinical data created doubt about their benefit for cancer patients, more encouraging data recently reported in myelofibrosis patients may promote additional applications of BET inhibitors in oncology as monotherapy and in combination with other therapeutic agents. Moreover, a growing number of approaches to optimize the therapeutic window by tinkering with the property profiles of BET inhibitors may provide additional clinical opportunities. This review provides an update on the status of ongoing activities to exploit BET bromodomain inhibition as a mechanism for cancer therapy.