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.
Dr. Shariska Petersen is a postdoctoral fellow in the Translational Research in Ovarian Cancer Laboratory at the University of Kansas Cancer Center and the first Gynecologic Oncology Fellow at the University of Kansas Medical Center. She received her Bachelor of Arts in Biological Sciences from the University of Chicago, where she conducted research on high-throughput protein kinase assays. She then completed a Post Baccalaureate Fellowship at the National Institutes of Health’s National Heart, Lung and Blood Institute where she studied cell trafficking and clathrin-independent endocytosis. She matriculated to the UCLA/Drew Medical Education Program, where she received her Doctorate of Medicine and completed her research thesis in cancer health disparities. During medical school, she received the American Medical Association’s Minority Scholar Award and scholarships from National Medical Fellowships, Inc. Dr. Petersen completed her Obstetrics and Gynecology residency training at Henry Ford Hospital/Wayne State University Program, where she received awards for scholarly activity and best practices in the art of medicine.
Additionally, Dr. Petersen was a 2017 AACR Scholar in Training and has presented her work at several national conferences. She is interested in drug synergy in ovarian cancer treatment as well as health disparities in gynecologic cancers. Her research will focus on PARP-inhibitor drug combinations for patients with homologous recombination proficient serous ovarian cancers.