Associate Professor of Medicine
Harvard Medical School
Co-Investigators: Ross Berkowitz, MD, and Zhigang Charles Wang, MD, PhD, Dana-Farber Cancer Institute and Brigham & Women's Hospital/Harvard Medical School, Boston, MA
With BCRF support, physicians and scientists have joined forces at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital to study the common genetic features of breast and ovarian cancers. This team believes that they can accelerate progress by studying these cancers together and hope to leverage discovery in one disease to benefit the other. The Dana-Farber/Brigham and Women’s team is using all available information from collaborative clinical trials, publicly available data from consortia of investigators around the world, and unique technologies that they themselves and their collaborators are developing.
Drs. Berkowitz, Matulonis, and Wang published two research reports showing the burden of genetic mutations that accumulate in breast and ovarian cancers influence the outcome of treatment. Specifically, they found that cancers with higher mutation burdens respond better to certain treatments, and live longer without cancer. This work has already been cited in high-profile reviews and scholarly articles. In ovarian cancer and certain breast cancers, two drugs are particularly useful and interesting. The first one is cisplatin, a platinum-based chemotherapy, and includes several derivatives that are used in both breast and ovarian cancer. The second group of drugs is comprised of newer agents called PARP inhibitors, which target the ability of cells to repair damaged genes and DNA. This team believes that the ability of breast and ovarian cancers to quickly repair their damaged DNA confers resistance to these agents; cancers that cannot repair as well build up damage and are more likely to be killed. They will test this hypothesis in a clinical trial that will study ovarian cancer tissue from patients receiving both drugs.
This team found that the amount of chromosomal damage in both triple-negative breast cancer and high-grade serous ovarian cancer predicted what the cancer response to cisplatin chemotherapy would be. The more unstable the DNA of the tumor is, the more sensitive to chemotherapy. “PARP” is an enzyme involved in aspects of DNA repair, and PARP inhibitors are now in clinical studies for the treatment of advanced ovarian cancer, specifically the high grade serous type. The researchers analyzed chromosomal patterns in an early-phase (Phase I) study of PARP inhibitors for women with advanced ovarian cancer. Investigators in Boston and other sites are completing a Phase II trial of PARP inhibitors (combined with another targeted drug), and this team proposes to complete genetic analysis of these cancers and relate their findings to the responsiveness of these cancers to PARP inhibitor treatment. They also located a very interesting genetic region which becomes altered in certain ovarian cancers and may cause or contribute to the cisplatin resistance that usually develops in ovarian cancer. They are excited to explore this genetic alteration further and to complete their study of the women participating in the PARP inhibitor trial.
Ursula Matulonis, MD is an Associate Professor of Medicine at Harvard Medical School and the Medical Director and Program Leader of the Gynecologic Oncology Program at Dana-Farber Cancer Institute. Her research is focused on gynecologic malignancies, and she is the Principal Investigator of several clinical trials for ovarian and cervical cancer. These trials include novel drug development as well as tissue banking and quality of life studies within ovarian cancer. Dr. Matulonis also has a strong interest in ovarian cancer translational research projects, two of which involve the molecular profiling of ovarian serous cancers as well as identification of oncogenic, targetable mutations in ovarian cancers.
Dr. Matulonis is a recipient of the Dennis Thompson Compassionate Care Scholar award, and was named one of Boston's "Best Physicians" in Medical Oncology by Boston Magazine. She also received two Partners in Excellence Awards for her steadfast work at Dana-Farber.
Dr. Matulonis currently serves on the National Comprehensive Cancer Network Ovarian Cancer Recommendation and Guideline Committee, the Society of Gynecologic Oncology National Meeting Planning Committee, the American Society of Clinical Oncology Education Committee for Gynecologic Oncology, the Gynecologic Oncology Group Quality of Life Committee, and is the Medical Director and Advisor for the non-profit organization Ovations for the Cure.
After receiving her MD from Albany Medical College in New York she completed an internship and residency at the University of Pittsburgh, followed by a medical oncology fellowship at Dana-Farber. She has been an attending physician at both Dana-Farber and Brigham and Women's Hospital since 1994.