Dana-Farber Cancer Institute
Associate Professor of Medicine
Director of Translational Research, Gynecologic Oncology
Harvard Medical School
Improving response to PARP inhibitors in breast and ovarian cancer.
Some triple-negative breast cancers (TNBC) 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 or ovarian cancers.
Drs. Konstantinopoulos and Matulonis have made significant progress developing new treatment strategies for breast and ovarian cancer. The team has multiple clinical trials in progress testing new treatment strategies. During the past year, the trials have yielded several new key findings. The team has successfully tested combination therapies against estrogen receptor (ER)-positive breast and ovarian cancers. The results of a phase II trial led by Dr. Matulonis testing the antibody-drug conjugate mirvetuximab soravtansine for recurrent ovarian cancer resulted in the accelerated approval of mirvetuximab soravtansine for platinum-resistant ovarian cancer in November 2022. This was the first new drug approved for ovarian cancer by the United States Food and Drug Administration since 2014.
In the upcoming year, Drs. Konstantinopoulos and Matulonis will continue to work on drugs that exploit a cancer cell’s underlying DNA repair problems but also develop new agents and new strategies targeting cell signaling pathways. The team will be completing PARP inhibitor combination studies and launching several new studies and research projects for both ovarian and endometrial cancer.
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.
The Play for P.I.N.K. Award in Honor of Laura Lassman and in Memory of Nicholas Lassman
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