PARP inhibitors are a promising new class of drugs for the treatment of ovarian cancer. They work by taking advantage of a cancer’s inability to repair its own DNA. Ovarian cancers from women who carry mutations in the DNA repair genes BRCA1 and BRCA2 have defective DNA repair, and are uniquely susceptible to PARP inhibitors. Mutations in other genes affecting DNA repair, either those that are inherited or those that develop within cancers may also predict response to PARP inhibitors. Other measurable features within the tumor may also predict response.
We seek to measure multiple biomarkers in both blood and tumors in order to predict response to PARP inhibitors. We will do this by assessing blood and tumor samples from women enrolled in a clinical trial of the PARP inhibitor rucaparib for recurrent ovarian cancer. We will use advanced genomic sequencing to test blood and tumors for mutations in a panel of 56 DNA-repair genes, along with other changes that might predict defective DNA repair. We will then look at those findings to see which features were most predictive of responding to the PARP inhibitor on the clinical trial. We hope to use these data to develop clinically useful tests to predict which women with ovarian cancer will have the best chance of responding to a PARP inhibitor, to allow the most rational and cost effective use of this promising therapy.
This grant was made possible in part by a generous donation from Ovarian Cycle Chicago.
Dr. Barbara Stulken Norquist received a Bachelor of Science degree in Biology from the University of Washington in 1999. She then graduated with honors from the University of Washington School of Medicine in 2004, and went on to a residency there in obstetrics and gynecology (2004 – 2008). Following residency, she completed a fellowship in gynecologic oncology (2008 – 2012). She subsequently joined the faculty at the University of Washington in 2012 in the department of Obstetrics and Gynecology, Division of Gynecologic Oncology, and is now an Assistant Professor. Her clinical duties include the care of women with known or suspected gynecologic malignancies, but with an additional focus on those with genetic susceptibility to ovarian cancer.
Her previous research examined the molecular pathogenesis of ovarian cancer as well as secondary genetic changes within tumors that promote resistance to chemotherapy. Her current research focus is on ovarian cancer genomics. In collaboration with Dr. Elizabeth Swisher and Dr. Mary Claire King, she is utilizing massively parallel sequencing techniques in order to identify novel genes in ovarian cancer and to identify biomarkers of chemotherapy response. She recently received a Marsha Rivkin Center for Ovarian Cancer Research Scientific Scholar Award to examine the emerging role of mutations in genes other than BRCA1 and BRCA2 in hereditary ovarian cancer. Her goals are to identify improved strategies for the prevention and treatment of ovarian cancer through genetic biomarkers.