2018 Early Career Investigator Grant Recipient — Katherine Fuh, MD, PhD

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

Associate Professor, Department of Obstetrics and Gynecology Director of Basic and Translational Research, Division of Gynecologic Oncology Washington University, St. Louis Katherine C. Fuh MD, PhD, is Associate Professor in the Department of Obstetrics and Gynecology at Washington University, St. Louis. She is also the Director of Basic and Translational Research for the Division of Gynecologic Oncology. She is an active member of the Alvin J. Siteman Cancer Center Mechanisms of Cancer Biology Program (MCBP). She also serves on the Admissions and Steering Committee for the Cancer Biology (CB) PhD program at Washington University, St. Louis. Dr. Fuh directs a translational lab that focuses on ovarian and uterine cancer particularly in novel therapeutics and improving sensitivity to chemotherapy incorporating the tumor microenvironment. Her laboratory work has resulted in development of clinical trials for the treatment of ovarian cancer. She graduated from Johns Hopkins University and obtained her M.D. at Georgetown University School of Medicine. She then completed her residency in obstetrics and gynecology at Stanford University and then entered the combined Gynecologic Oncology fellowship program at University of California/San Francisco (UCSF) and Stanford. She is a graduate of the ARTS (Advanced Residency Training at Stanford) program. During this time, she combined clinical fellowship with advanced research training to complete a PhD degree in Cancer Biology at Stanford University. She was also a NIH-supported Reproductive Scientist Development Program (RSDP) Scholar. Dr. Fuh’s research on ovarian cancer has been funded by the National Cancer Institute (NCI), American Cancer Society (ACS), Mary Kay Foundation, Foundation for Women’s Cancer (FWC), American Board of Obstetrics and Gynecology (ABOG), and Gynecologic Oncology Group (GOG) Foundation. She serves on study sections for the NCI and Department of Defense Ovarian Cancer Research Program.