Ovarian cancer is unusual among intra-abdominal epithelial cancers in that it only rarely spreads through the bloodstream to different sites. More commonly, ovarian cancer spreads locally in the abdominal cavity. Recent work in Dr. Swisher’s laboratory identified tumor-specific, cell-free DNA in the plasma of patients with ovarian cancer. One third of ovarian cancer patients had circulating tumor-specific DNA. Circulating tumor DNA was correlated with worse survival rates and the development of subsequent brain metastases. She proposes that alterations in factors that cause angiogenesis, or new blood vessel growth, explain the worse prognosis and increased metastatic potential of cases with circulating tumor DNA. Angiogenesis is critical in tumor growth and metastasis, allowing tumor cells access to nascent blood vessels. Angiogenic factors have been associated with poor prognosis in ovarian cancer. In her study, she will examine the stability of the small blood vessels near and within ovarian cancers and assess expression of genes and proteins involved in ovarian cancer angiogenesis in two groups of ovarian cancers: those from patients with circulating tumor DNA and those without. She expects that tumors from women with free tumor DNA in plasma will show decreased vessel stability and alterations in angiogenic factor gene expression that correlate with worse survival. The lack of understanding of ovarian tumor biology and metastasis has hindered efforts to improve survival, as most women relapse and die of chemoresistant disease. Testing the relationship of free tumor DNA in plasma and ovarian tumor angiogenesis will provide a previously unexamined basis from which to gain unique insights into ovarian tumor biology.
Dr. Swisher is a Professor in the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology and Adjunct Professor in the Department of Medicine, Division of Medical Genetics at the University of Washington. She graduated with a B.S. from Yale University and received her M.D. from the University of California at San Diego. She completed her residency at the University of Washington in Ob/Gyn and a fellowship in Gynecologic Oncology at Washington University St Louis. Both her clinical and laboratory work focus on cancer genetics. She is medical director of the Breast and Ovarian Cancer Prevention Program at the Seattle Cancer Care Alliance. The primary focus of Dr. Swisher’s lab is to study the molecular genetics of ovarian cancer, including understanding the early events of ovarian tumorigenesis and development of novel biomarkers of disease and prognosis. Recently, she has used massively parallel sequencing to identify a broader inherited component of ovarian, fallopian tube and peritoneal cancers than previously appreciated with the goal of allowing targeted prevention in at risk women. She has been applying targeted deep sequencing to ovarian cancers with the goal of personalizing therapeutic choices. The OCRF grant will support the collaboration of Dr. Swisher’s group with that of Scott Kaufmann M.D. PhD and Paul Haluska M.D. PhD, both of the Mayo Clinic in the effort to develop biomarkers that predict response to PARP inhibitors and platinum chemotherapy.