The MCW Cancer Center has awarded Elizabeth Hopp, MD, Assistant Professor of Gynecologic Oncology, an Our Patient Project (OPP) pilot grant totaling $458,577 over four years for her project, Identification of Targeted Treatments for Adult-Type Granulosa Cell Tumors of the Ovary (AGCT) through In-depth Multi-omics Analysis. OPP is an important translational research element of the center’s Precision Oncology high-impact initiative; a main goal of the program is to address a major unmet need in cancer research to better serve patients across the community. Dr. Hopp’s innovative study will bring together a multidisciplinary team of scientists, oncologists, and Shared Resources experts to help drive discovery of more effective treatments for AGCT, a rare disease that comprises approximately 5% of all ovarian cancer cases.
“Approximately 33% of patients with AGCT will relapse and 50-80% of patients will die from their recurrent cancer. Those with recurrent disease often have multiple different chemotherapy treatments and undergo multiple surgeries. However, the treatments we currently have for this cancer are inadequate. My research aims to discover new, effective, and tolerable therapies for recurrent and metastatic AGCT,” said Dr. Hopp.
AGCT are sex-cord stromal tumors that differ from epithelial ovarian cancer (the most common type) by having a unique mutation in a gene called FOXL2, which is present in about 97% of tumors. “AGCT have a very insidious course that causes survival outcomes to become less favorable with each increasing stage. The average time to recurrence is approximately four years, however, recurrences have been reported up to 40 years after diagnosis. This requires long-term surveillance,” explained Dr Hopp.
To help improve outcomes for patients affected by the disease, Dr. Hopp and study co-investigators Pradeep Chaluvally-Raghavan, PhD, Associate Professor of Obstetrics & Gynecology, and Janet Rader, MD, Chair of Obstetrics & Gynecology, aim to accomplish the following:
- Characterize the functions of the FOXL2 mutation in AGCT; the team will develop a mutant FOXL2 antibody to the determine molecular functions of mutant FOXL2. They will use ChIP-seq and ATAC-seq to identify differential target genes regulated by mutant FOXL2 along with putative regulatory elements.
- Uncover actionable pathways in AGCT to discover drug targets for recurrent and metastatic disease; the team hypothesizes there are undiscovered actionable targets within the sex steroid pathways. To test this hypothesis, they will utilize the large institutional banked cohort of AGCT specimens along with their patient-derived AGCT cell lines. They will also perform RNA sequencing.
- Develop a collaborative database and tissue bank for AGCT; the team will develop an online survey to identify personal and environmental risk factors in AGCT. They will also create a social media platform for subject recruitment, engagement of the AGCT community, and sample collection.
The study will also leverage several MCW shared resource cores, including the Biorepository and Tissue Analytics Shared Resource, Center for Biomedical Mass Spectrometry Research, and Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine.
Dr. Hopp said her current research, both in cell lines and in a group of patients, has shown promising results with a combination of anti-hormonal treatments to produce complete hormonal blockade based on the biology of the cancer. She’s grateful that the OPP grant may help to expand these results, and ultimately lead to drug trials for recurrent, metastatic AGCT and improved survival for patients everywhere.
“Results from this study can be used to inform future clinical trials for women with AGCT, and can help to establish effective novel therapies. The findings will also be used to propel future funding avenues for this research area through the National Institutes of Health. My goal is to establish MCW as a focused center for AGCT research,” said Dr. Hopp.
The research team thanks the MCW Cancer Center for providing OPP funding support to advance this important work. They also thank their collaborators Dr. Juan Felix, Dr. Anjishnu Banerjee, Dr. Victor Jin, and Dr. Shirng-Wern Tsaih (Research Scientist), who will be integral to accomplishing the study’s goals and making a positive impact on patients with ACGT.
Learn more about MCW Cancer Center pilot funding.