Ovarian Cancer is the deadliest gynecologic cancer in the United States. Treatment options for women diagnosed with ovarian cancer have recently expanded to include Poly ADP ribose polymerase (PARP) inhibitors. PARP inhibitors work best in women who have been diagnosed with ovarian cancer caused by BRCA (BReast CAncer susceptibility gene) mutations. A subset of women, who do not have BRCA mutations often have worse outcomes due to increased expression of genes Cyclin E and Bromodomain and extraterminal 4 (BDR4). Unfortunately, many of the women with these subtypes of ovarian cancer do not respond well to PARP inhibitors.
The Translational Research in Ovarian Cancer (TROC) laboratory at The University of Kansas Cancer Center and others have shown that inhibition of BDR4 with Bromodomain extraterminal motif (BET) inhibitors, can cause tumors to respond to PARP inhibitors. After treatment with BET inhibitors, tumors behave as if they have a BRCA mutation which makes them more responsive to PARP inhibitors. This was an exciting result because treating women who do not have BRCA mutations with both PARP and BET inhibitors may improve outcomes. Our goal is to determine which women would benefit from BET and PARP inhibitor combination therapy.
Our objective is to determine if levels of Cyclin E and BRD4 help us determine which women will respond to this new combination. Ultimately, we strive to use Cyclin E and BRD4 levels to determine which women will benefit from BET and PARP inhibitor combination therapy. These results will be directly applicable to clinical trials of BET and PARP inhibitors with the primary objective of improving clinical outcomes for women who currently do not have effective treatment options.