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Panagiotis Konstantinopoulos, MD, PhD
Associate Professor of Medicine
Director of Translational Research
Harvard Medical School
Dana-Farber Cancer Institute
Goal: To improve response to PARP inhibitors in breast and ovarian cancer.
Impact: Drs. Konstantinopoulos and Matulonis 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. Konstantinopoulos and Matulonis 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. Konstantinopoulos and Matulonis are studying PARP inhibitor combination therapies that may act synergistically to provide better treatment outcomes for patients with breast and/or ovarian cancers. It is their goal to move promising combinations into larger clinical trials.
Current research: Drs. Konstantinopoulos and Matulonis 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. These studies may lead to translational work with the most promising PARP inhibitor combinations.
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 continue to develop new 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 will move promising combinations into larger clinical trials.
Panagiotis A. Konstantinopoulos, MD, PhD is Director of Translational Research and Attending Oncologist in the Gynecologic Oncology Program at Dana-Farber Cancer Institute, and an Associate Professor of Medicine at Harvard Medical School. His translational research career focuses on ovarian cancer and other gynecologic malignancies with an important niche in the areas of DNA damage and repair and immunotherapy. His work has focused on unraveling mechanisms of resistance to chemotherapy and targeted agents, developing the rationale and preclinical data for novel drug combinations in ovarian cancer, and identifying novel diagnostic and predictive biomarkers of therapeutic response in gynecologic cancers as well investigating their mechanistic implication in carcinogenesis.
His research efforts in this area have been supported by several Harvard-wide, industry and national sources including the Department of Defense (DOD), Ovarian Cancer Research Program (OCRP) and the American Association of Cancer Research (AACR). As a clinical researcher, he is also involved as a principal investigator (PI) and co-investigator in several gynecologic cancer clinical trials. Dr. Konstantinopoulos has served as a member of the Editorial Board of Journal of Clinical Oncology, is co-chair of the Dana Farber Harvard Cancer Center (DFHCC) Audit Committee and a member of the Gynecologic Oncology Group (GOG) Experimental Medicine Committee.