Abstract A18: Development of a novel peptide therapeutic that targets ovarian cancer via the tumor microenvironment

Abstract

Abstract Ovarian cancer is the most lethal gynecologic malignancy and the fourth leading cause of cancer deaths in women. Pathologically, ovarian cancer is categorized into multiple subtypes, with epithelial ovarian cancer (EOC) representing 90% of cases. Despite our increased understanding of the biology governing the progression of EOC the survival rate for patients with stage IV EOC is only 17%. The vast majority of ovarian cancer-related deaths are caused by metastatic dissemination of cells from the primary tumor resulting in subsequent organ failure. Tragically, there are no clinically approved drugs that have shown significant efficacy at treating advanced, metastatic, ovarian cancer. As such, there is a dire need for efficacious therapies that can specifically treat advanced, metastatic ovarian cancer. We were the first to identify prosaposin (psap) as a potent inhibitor of tumor metastasis via stimulation of the anti-tumorigenic protein thrombospondin-1 (Tsp-1) in bone marrow-derived cells that are recruited to metastatic sites. We report here that virtually 100% of human serous ovarian tumors tested express CD36, the receptor that mediates the pro-apoptotic activity of Tsp-1. Accordingly, we developed a novel cyclic peptide with drug-like properties derived from the active sequence in psap. Strikingly, this cyclic psap peptide was able to significantly regress metastatic tumors in a patient-derived tumor xenograft (PDX) model of metastatic ovarian cancer. Thus, our findings suggest that development of a therapeutic agent based on this psap peptide would have significant efficacy in treating patients with metastatic ovarian cancer. Citation Format: Suming Wang, Anna Blois, Tina EI Rayes, Joyce F. Liu, Michelle S. Hirsch, Karsten Gravdal, Diane R. Bielenberg, Lars A. Akslen, Ronny Drapkin, Vivek Mittal, Randolph S. Watnick. Development of a novel peptide therapeutic that targets ovarian cancer via the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A18.