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Panagiotis Konstantinopoulos, MD, PhD
Associate Professor of Medicine
Director of Translational Research
Harvard Medical School
Dana-Farber Cancer Institute
- Studies are focused on improving response to PARP inhibitor therapy in breast and ovarian cancer.
- Laboratory and clinical studies are conducted to test combination approaches to improve response to PARP inhibitors.
- These studies may benefit patients with triple negative breast cancer, as TNBC tumors share common biology with ovarian cancer.
Ovarian cancer is an aggressive disease with few treatment options. A class of drugs called PARP inhibitors has been approved for treatment of ovarian cancers caused by mutations in the BRCA genes. Resistance to PARP therapy, however, reduces the clinical benefit of these drugs. Drs. Konstantinopoulos, Berkowitz, and Matulonis are studying ways to increase the effectiveness of PARP inhibitors for patients with ovarian cancer as well as an aggressive form of breast cancer called triple negative.
Full Research Summary
Drs. Konstantinopoulos, Berkowitz, and Matulonis have joined forces to study the common genetic features of breast and ovarian cancers. Using information from collaborative clinical trials, publicly available data from researchers 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. With the expanded use of PARP inhibitors following FDA approvals in recurrent ovarian cancer and breast cancer, the Dana Farber/ Brigham and Women's Hospital team is focused on understanding and overcoming the underlying mechanisms that allows the cancer cell to become resistant to PARP inhibitors.
They are conducting laboratory studies to test combination strategies that if found promising will be further tested in clinical trials. Of particular interest are combinations of PARP inhibitors with other biologic agents that inhibit DNA repair that can convert a cancer cell from one that can repair DNA (and is resistant to PARP inhibitors) into one that does not repair DNA.
With the approval of olaparib (Lynarza®) for advanced BRCA breast cancer–most of which are of the triple negative subtype, findings from these studies have the potential to benefit more patients with aggressive breast and ovarian cancers.
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.