Abstract 4071: Utilizing colforsin as a novel therapeutic for high grade serous ovarian cancer treatment

Abstract

Abstract Epithelial ovarian cancer (EOC) is currently the deadliest gynecological cancer with approximately 20,000 new cases and 15,000 deaths per year in the United States. Ovarian cancer can be stratified into distinct subtypes of which high-grade serous ovarian cancer (HGSOC) comprises 90% of all cases. The majority of HGSOC patients are diagnosed with late-stage disease and have a poor prognosis with a 5-year survival rate of less than 30%. Thus, there is a critical need to develop novel therapeutic strategies to improve patient treatment and survival outcomes. Our lab has recently discovered that the small molecule colforsin has potent anti-cancer properties when used to treat HGSOC in vitro and in vivo. Colforsin is a water-soluble derivative of forskolin, and acts as an activator of cAMP signaling via direct binding and activation of adenylyl cyclase. It is currently in clinical use for treatment of conditions such as glaucoma, diabetes, and liver fibrosis. This makes colforsin a prime candidate for drug repurposing to treat ovarian cancer. Our data show that colforsin can induce cell cycle arrest and cell death in established HGSOC cell line models in vitro. We have also found that colforsin can inhibit tumor growth and tumor burden in an intraperitoneal model of HGSOC using HEYA8 cells. In addition, we have also found that colforsin acts synergistically with cisplatin to cause HGSOC cell death. Taken together, our data show that colforsin has potential as a new therapeutic tool to aid in HGSOC treatment in combination with existing therapies. Citation Format: Matthew Knarr, Hunter Reavis, Marilyn Mitchell, Ronny Drapkin. Utilizing colforsin as a novel therapeutic for high grade serous ovarian cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4071.