William H. Baker Professor of Gynecology
Chief of Gynecologic Surgery
Brigham and Women's Hospital/Harvard Medical School
Studies are focused on improving response to PARP inhibitor therapy in breast and ovarian cancer.
Genomic analysis of ovarian tumors is being conducted to identify biomarkers of response to PARP inhibitors.
These studies may benefit patients with triple negative breast cancer, as TNBC tumors share common biology with ovarian cancer.
Drs. Berkowitz, Matulonis and Konstantinopoulos have joined forces to study the common genetic features of breast and ovarian cancers. The Dana-Farber/Brigham and Women's team is credited with showing that the accumulation of genetic mutations in breast and ovarian cancers influences how the tumors respond to treatment.
Using information from collaborative clinical trials, publicly available data from researchers from around the world, and emerging technologies, they are leveraging discoveries made in one disease to benefit the other. They then use this information to better understand drug resistance and to identify new biomarkers and therapeutic targets.
PARP inhibitors are a class of drugs that interfere with repair of damaged DNA and have been effective in ovarian cancers that harbor BRCA mutations. Resistance to PARP inhibitors is a very important clinical problem, however.
The group recently identified at least four unique genomic alterations that are associated with sensitivity or resistance to PARP inhibitors, including down-regulation of a key molecule called RAD51, which increases sensitivity of ovarian cancer to PARP inhibitors, and a phenomenon called PTEN homozygous deletion, which is common in triple-negative breast cancer (TNBC) and promotes drug resistance.
Over the next year, they will generate PARP inhibitor-resistant tumors in their experimental models and attempt to find a way to restore their sensitivity. Because PARP inhibitors are being tested in TNBC, they believe their findings in ovarian cancer may be valuable for predicting response to PARP inhibitors in TNBC as well. This work will continue to shed light on resistance mechanisms and provide biomarkers of treatment response.
Ross Berkowitz, MD is the William H. Baker Professor of Gynecology at Harvard Medical School and the Director of Gynecology and Gynecologic Oncology at Dana-Farber Cancer Institute and Brigham and Women's Hospital. In addition, he is also the Co-Director of the Women's Cancers Program at Dana-Farber and the Director of the Gynecologic Cancer Program at Dana-Farber/Partners Cancercare and Dana-Farber/Harvard Cancer Center.
During the past twenty years, the focus of his research has been in the areas of gestational trophoblastic disease and ovarian neoplasia. Investigations in gestational trophoblastic disease have dealt with identifying risk factors for development of these tumors as well as advancing understanding of the natural history of these diseases including subsequent reproductive experience. His research in ovarian neoplasia has concerned both the development of innovative and novel therapies as well as molecular biologic studies to identify genetic changes in ovarian neoplasia and differences in the pathways of development of borderline ovarian tumors, invasive ovarian cancers, and peritoneal cancers.
Dr. Berkowitz earned his MD from Boston University and had his residency training in surgery at the Peter Bent Brigham Hospital and then in obstetrics and gynecology at the Boston Hospital for Women. He completed his fellowship in gynecologic oncology at the Boston Hospital for Women and joined the faculty at Brigham and Women's Hospital thereafter.