Sarah Beth Gitto, PhD
University of Pennsylvania
2019 Scientific Scholar Award
Priming the TME with anti-VEGF to enhance the efficacy of dual checkpoint inhibition in PARPi-resistant OC
Recent studies have shown that the use of the PARP inhibitor olaparib increases survival of ovarian cancer. Unfortunately, most patients will become resistant to PARP inhibitors, thus novel treatment strategies are critical for these patients. The presence of immune cells known as tumor-killing T-cells in tumors are associated with better survival in ovarian cancer. Developing therapies that control the surrounding tumor microenvironment and help recruit tumor-killing T-cells to the tumor may be an effective treatment strategy. Additionally, drugs known as immune checkpoint inhibitors have shown promising results in other cancer types, but have not been as effective against ovarian cancer. In this study, Dr. Gitto investigates the modification of the tumor microenvironment to allow tumor-killing T-cells access to the tumor prior to treatment with immune checkpoint inhibitors, to treat PARP inhibitor resistant ovarian cancer. The physical and chemical barrier surrounding the tumor makes it difficult for tumor-killing T-cells to infiltrate the tumor. The VEGF protein promotes tumor survival through increasing tumor blood supply and stimulating a pro-tumor immune response, preventing tumor-killing T-cells from infiltrating the tumor and killing cancer cells. Dr. Gitto proposes that treating ovarian cancers with a VEGF protein inhibitor, known as Bevacizumab, may reduce the physical and chemical barriers that inhibit T-cells from killing tumor cells. Bevacizumab has been approved for front-line therapy in combination with chemotherapy for ovarian cancer and has shown to have some promising anti-tumor effects when combined with immune checkpoint inhibitors in other cancers. Dr. Gitto will investigate how prior treatment with Bevacizumab may enhance the effectiveness of immune checkpoint inhibitors to treat PARP inhibitor resistant ovarian cancers in a mouse model.