2018 Recipient Katherine Fuh, MD, PhD

Katherine Fuh, MD, PhD

Inhibition of Metastasis in BRCA2-associated Ovarian Cancers

Project Summary

In the 1990s, 40% of women with epithelial ovarian cancer (by far the most common type of ovarian cancer) lived for five years after their cancer was discovered. Despite many years of work by researchers all over the world, today the percentage of women surviving five years has only increased to 46%. The high rate of ovarian cancer death is largely because most patients are initially diagnosed after their cancer has already spread to other sites in the body, or their cancer spreads despite therapy. In recent years, the best outcomes have been in the 25% of patients who have ovarian cancer in which either the BRCA1 or the BRCA2 genes are mutated. Women with these tumors are treated with drugs that inhibit the gene poly-ADP ribose polymerase (PARP). However, although this drug causes the tumor cells to stop multiplying, these tumors eventually spread to other sites in the body, and only 35% of these patients live for 10 years. Thus, we must find new ways to treat the 1,100 women diagnosed with BRCA2-mutant ovarian cancer each year.

Our study takes a new approach to developing treatments for ovarian cancer. Instead of focusing on the ability of tumor cells to multiply, we focus on their ability to spread to other sites in the body. Additionally, we examine the interactions between the tumor and the surrounding tissue in the body, which the tumor uses to support its growth and spread. Here, we propose to determine the role of the gene Discoidin domain receptor 2 (DDR2) in ovarian tumors with mutations in BRCA2. We chose DDR2 because we have strong preliminary data indicating that this gene is involved in cancer spread in ovarian tumors that do not have mutations in BRCA2. Additionally, we found that tumors with mutations in BRCA2 produce a lot of the protein encoded by the DDR2 gene. We propose to address three questions about DDR2. First, what role does this gene play in helping tumors spread, and does the level of DDR2 protein made by ovarian tumors correlate with patients’ survival? Second, can a novel DDR2 inhibitor that we have developed prevent tumor spread? Third, does DDR2 in the non-tumor cells of the body help the tumor spread? To answer these questions, we will examine human tumors and perform experiments both in cells outside of the body and in mice. Long term, our studies will lead to clinical trials in which the PARP inhibitor will be combined with a DDR2 inhibitor to try to improve survival of ovarian cancer patients with mutations in BRCA2. Additionally, by understanding the role of DDR2 in ovarian cancer spread and in non-tumor cells, our work will lead to improvements in treatment for all ovarian cancer patients.

This research has been generously supported by Newk’s Cares, and Ovarian Cycle, Jackson, MS.

Bio

Katherine C. Fuh, MD, PhD is an Assistant Professor in the Division of Gynecologic Oncology at Washington University, St. Louis. She received a BA in Biology at Johns Hopkins University. She received her MD from Georgetown Medical School and her PhD in Cancer Biology from Stanford University Medical School with Amato Giaccia as her PhD advisor. She completed her residency in Obstetrics and Gynecology at Stanford Hospital and then entered the combined Gynecologic Oncology fellowship program at Stanford and University of California, San Francisco (UCSF). In 2013, she was awarded a position as a scholar on the NICHD K12-Reproductive Scientist Development Program (RSDP) with Greg Longmore, MD in Medical Oncology as her mentor. Her research interests and laboratory focuses on identifying and validating therapeutic targets in ovarian cancer metastasis in the context of the tumor microenvironment. Her work has been recognized with awards such as the American Cancer Society Institutional Research Grant, Washington University Siteman Cancer Center Cancer Frontier Fund, RSDP Research Support and Seed Grants (supported by American College of Obstetricians and Gynecologists-ACOG, Burroughs Wellcome Fund, March of Dimes), and Mary Kay Foundation. She is faculty member in the Molecular Cell Biology Ph.D. Program in the Division of Biology and Biomedical Sciences (DBBS) at Washington University, a member of the Cell-to-Cell Communications in Cancer Research Program (C4P) at Siteman Cancer Center, associate member of the Integrating Communications within the Cancer Environment (ICCE), and a member of the Center for Reproductive Health Sciences (CRepHS).