SU2C-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Ovarian Cancer Dream Team: DNA Repair Therapies for Ovarian Cancer
Elizabeth M. Swisher, MD
Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology
Medical Director, Breast and Ovarian Cancer Prevention Program
Seattle Cancer Care Alliance
Alan D. D’Andrea, MD
Chief, Division of Genomic Stability and DNA Repair
Harvard Medical School
Alvan T. and Viola D. Fuller American Cancer Society Professor of Radiation Oncology
Dana-Farber Cancer Institute
Overview
Ovarian cancer is usually diagnosed at an advanced stage, when it is hard to treat and death rates are high. Cancers with certain types of DNA repair defects are responsive to targeted therapies, such as drugs called PARP inhibitors.
The Dream Team brought together internationally renowned experts to focus on developing new therapies that target DNA repair and on expanding the use of drugs called PARP inhibitor to a much larger group of women. In addition, by screening for inherited mutations in genes linked to DNA repair, the team worked to find ways to identify women at higher risk for ovarian cancer. The team has taken a three-pronged approach to its goals:
- Identify ovarian cancers that are likely to respond to DNA repair therapies.
- Evaluate, in three clinical trials, new drug combinations that may sensitize ovarian tumors to PARP inhibitors.
- Develop web-based genetic testing and counseling strategies and test surgical prevention models.
Progress to Date
The Dream Team has made significant progress in the completion of its scientific aims:
- Identified new DNA repair biomarkers which will contribute to predicting PARPi sensitivity or resistance. The team deployed these biomarkers, and functional tests for HR and fork stability, in short-term ovarian cancer organoid cultures, suitable for predicting drug response.
- Analyzed the results of a Phase 2 combination of PARPi plus anti-PD1 antibody.
- Opened the MAGENTA and WISP programs to develop web-based genetic testing and counselling strategies for ovarian cancer risk, providing access to more women in the community, and test fallopian tube removal as a surgical approach to reduce risk that will avoid forced menopause by preserving a woman’s ovaries.
Amount of Funding
$6 million
Principals
- Gini F. Fleming, MD, The University of Chicago
- Scott H. Kaufmann, MD, PhD, Mayo Clinic, Rochester
- Maria Jasin, PhD, Memorial Sloan Kettering Cancer Center
- Karen H. Lu, MD, MD Anderson Cancer Center
Advocates
Jamie Crase, ovarian cancer survivor and advocate
- Kathleen Gavin, Executive Director, Minnesota Ovarian Cancer Alliance
- Sue Friedman, executive director of Facing Our Risk of Cancer Empowered (FORCE)