Cancer

Cell culture and mouse studies suggest BET bromodomain proteins inhibitors could help treat SPOP-mutant endometrial cancer and mutant or wild-type SPOP prostate cancers. In a human endometrial cancer cell line, expression of endometrial cancer-associated SPOP mutations increased sensitivity to a BET inhibitor tool compound compared with wild-type expression. In xenograft mouse models of endometrial cancer, the BET inhibitor decreased growth of SPOP-mutant tumors, but not wild-type SPOP tumors, compared with vehicle. In human prostate cancer cell lines, expression of wild-type SPOP increased sensitivity to the BET inhibitor compared with expression of prostate cancer-associated SPOP mutations. Also in the mutant SPOP cells, AKT knockdown or the AKT inhibitor ipatasertib increased sensitivity to the BET inhibitor compared with normal AKT expression or vehicle. In mice with prostate cancer xenografts expressing mutant SPOP, ipatasertib plus the BET inhibitor decreased tumor volume compared with either agent alone. Next steps include additional studies to confirm that SPOP-mutant endometrial and prostate cancers are sensitive and resistant, respectively, to BET inhibitors...