Panagiotis Konstantinopoulos, MD, PhD

Developing new therapeutic strategies for breast and gynecologic cancers.

Impact

There is significant unmet therapeutic need for the two most common gynecologic cancers in the United States, ovarian and endometrial, have genetic overlap with certain types of breast cancer driven by mutations in the BRCA genes. Breast cancer survivors are at risk for these cancers because of inherited high-risk BRCA mutations, rising incidence of endometrial cancer in the United States, and increased risk of endometrial cancer caused by certain breast cancer treatments such as tamoxifen. Poly (ADP-ribose) polymerase (PARP) inhibitors, which target the underlying DNA repair problem, are not beneficial to all patients or the cancer will eventually become resistant to the treatment. Drs. Konstantinopoulos and Matulonis are developing combination therapies that may act synergistically to provide better treatment outcomes for patients with breast or ovarian cancers.

Progress Thus Far

Drs. Konstantinopoulos and Matulonis have multiple clinical trials in progress testing new treatment strategies. During the past year, the trials have yielded several new findings. A phase II study evaluating treatment with the PARP inhibitor talazoparib in combination with immunotherapy avelumab in patients with endometrial cancer that is DNA repair-deficient showed an overall response rate of 40 percent. Additionally, the results of a phase II trial led by Dr. Matulonis testing the chemotherapy letrozole combined with the CDK4/6 inhibitor abemaciclib in ER-positive recurrent endometrial cancer led to the addition of this combination to the National Comprehensive Cancer Network endometrial cancer guidelines in 2023.

What’s next

In the upcoming year, Drs. Konstantinopoulos and Matulonis will continue to develop new therapeutic strategies for the two most common gynecologic cancers in the U.S., ovarian and endometrial cancer, and continue to expand translational platforms to study these cancers. They will focus on designing and opening new trials for ovarian and endometrial cancers and analyzing the outcomes of their ongoing trials.