2018 Early Career Investigator Grant Recipient — Katherine Fuh, MD, PhD
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.
Associate Professor and Joh A. Kerner Chair in Gynecologic Oncology, Department of Obstetrics and Gynecology
Director of Translational and Basic Research, Division of Gynecologic Oncology
University of California, San Francisco
Katherine Fuh, MD, PhD is an Associate Professor and the Joh A. Kerner Chair in Gynecologic Oncology in the Department of Obstetrics and Gynecology at University of California, San Francisco. She is the Director of Translational and Basic Research for the Division of Gynecologic Oncology. She returns to UCSF in 2022 after 9 years on faculty at Washington University in St. Louis. 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 also 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.
She serves on national committees for clinical trials and translational research including Translational Co-Chair for the Uterine Corpus Committee for the NRG Clinical Trials Group. She is the international PI for GOG-3059/ENGOT OV-66 which is a Phase 3, Randomized, Double-Blind, Placebo-Controlled/Paclitaxel Study in Combination with Batiraxcept, an AXL inhibitor, for Platinum-resistant, High-Grade Serous Ovarian, Fallopian-Tube, and Peritoneal Cancer. She is the principal investigator on multiple grants from various federal and foundation sources. She is committed to developing better treatments for women with gynecologic cancers.