Therapeutics: BET bromodomain proteins; bromodomain containing 4 (BRD4); histone deacetylase (HDAC)

Mouse and cell culture studies suggest combining BRD4 inhibition with the HDAC inhibitor Zolinza vorinostat could help treat pancreatic cancer. BRD4 levels were higher in pancreatic tumors from a mouse model of the cancer than in pancreatic tissue from normal mice. In a human pancreatic cancer cell line, a tool compound that inhibits BET bromodomain proteins and Zolinza increased markers of apoptosis and decreased growth and BRD4 levels compared with either agent alone or vehicle. In a mouse xenograft model of pancreatic cancer, the BET inhibitor and Zolinza decreased tumor volume. Next steps include testing the combination of BET inhibition and Zolinza in other cancer models...