Ovarian cancer is usually diagnosed at an advanced stage, when it is hard to treat successfully and death rates are high. Progress toward new treatments has been slow. However, new information from genetic sequencing of high-grade serous ovarian cancers has revealed a common weakness, mutations that cause defects in biological pathways that repair damaged DNA. Cancers with certain types of DNA repair defects are responsive to specific targeted therapies, such as drugs called PARP inhibitors, one of which was recently approved by the U.S. Food and Drug Administration to treat ovarian cancer associated with deleterious germline mutations in either the BRCA1 or BRCA2 genes.
The SU2C-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team brings together internationally renowned experts in the science of DNA repair, translational investigators, and clinicians, across six institutions, to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science. The team will focus on developing new therapies that target DNA repair and expanding PARP inhibitor use to a much larger group of women, beyond those with BRCA1 and BRCA2 mutations. In addition, by screening for inherited mutations in genes linked to DNA repair, the team hopes to identify women at high risk for ovarian cancer for whom preventative measures may be lifesaving. With its combined focus on treatment and prevention this program is poised to deliver near-term ovarian cancer patient benefit.
The team will take a three-pronged approach to its goals. First, the researchers will apply cutting-edge DNA repair science to identify ovarian cancers most likely to respond to DNA repair therapies. Second, they will evaluate, in three clinical trials, novel drug combinations that may sensitize ovarian tumors to PARP inhibitors; if successful this would expand the use of these drugs. Third, they will develop web-based genetic testing and counseling 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.
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