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Ursula A. Matulonis, MD
Professor of Medicine
Harvard Medical School
Chief and Director, Division of Gynecologic Oncology
Dana-Farber Cancer Institute
Goal: To improve response to PARP inhibitors in breast and ovarian cancer.
Impact: Drs. Matulonis and Konstantinopoulos are developing and testing new combination treatments that could increase the effectiveness of PARP inhibitors. Their work could benefit patients with ovarian cancer and those who have triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that shares common biology with ovarian cancer.
What’s next: The team will continue to investigate treatment combinations that make cancer cells more responsive to PARP inhibitors.
PARP inhibitors are a type of therapy that was first approved to treat ovarian cancer—a disease which is genetically similar to breast cancer—and were subsequently approved to treat recurrent BRCA-associated breast cancer. Unfortunately, not all patients who respond to PARP inhibitors, and some develop resistance to them. Drs. Matulonis and Konstantinopoulos aim to identify drug combinations that will enhance the effectiveness of PARP inhibitors and find ways to overcome resistance.
Full Research Summary
Research Area: Identifying PARP inhibitor combinations that will work synergistically to treat ovarian and breast cancer patients.
Impact: Some triple negative breast cancers share a common biology with ovarian cancer driven by mutations in the BRCA genes and deficient DNA repair. Consequently, treatment approaches such as Poly (ADP-ribose) polymerase (PARP) inhibitors, which target the underlying DNA repair problem are currently being used to treat both ovarian and breast cancers with BRCA mutations. However, not all women will benefit from single agent PARP inhibitors or will develop resistance to the PARP inhibitor. Drs. Matulonis and Konstantinopoulos are studying PARP inhibitor combination therapies that may act synergistically to provide better treatment outcomes for patients with breast and/or ovarian cancers.
Current investigation: Drs. Matulonis and Konstantinopoulos are studying the effects of various combinations of PARP inhibitors with other novel targeted therapies such as immunotherapies to improve response to PARP inhibitor-based therapy. The team is leading several phase 2 or 3 clinical trials of PARP inhibitor combinations that inform treatment for both breast and ovarian cancers.
What she’s learned so far: The research team has examined various PARP inhibitor combinations, assessed the ability of these combinations to reduce PARP-based therapy resistance, and deciphered the underlying mechanisms of action.
What’s next: The team will complete and begin new projects testing PARP inhibitor combinations that could be used for women with ovarian or breast cancer whose cancers exhibit initial resistance to a single agent PARP inhibitor. They are moving promising combinations into larger clinical trials.
Ursula A. Matulonis, MD, is Chief and Director of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. She is the first recipient of the Brock-Wilson Family Chair at the Dana-Farber Cancer Institute. She co-leads the ovarian cancer program within the Dana-Farber/Harvard Cancer Center. Her research focuses on developing new targeted therapies for gynecologic malignancies, with a specific interest in ovarian cancer and endometrial cancer.
Dr. Matulonis has led several PARP inhibitor, anti-angiogenic agent, immunotherapy, and combination trials for ovarian cancer in the United States and internationally. Dr. Matulonis serves on the Massachusetts Ovarian Cancer Task Force, the NRG ovarian committee, and the Scientific Advisory Board for the Ovarian Cancer Research Foundation and the Clearity Foundation. She received the Dana-Farber Dennis Thompson Compassionate Care Scholar award, the Lee M. Nadler “Extra Mile” Award, the Clearity Foundation award, and the Zakim Award at Dana-Farber for patient advocacy.
After receiving her MD from Albany Medical College, she completed an internship and residency at the University of Pittsburgh, followed by a medical oncology fellowship at the Dana-Farber Cancer Institute in Boston, MA