Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment

Suming Wang, Anna Blois, Tina El Rayes, Joyce F. Liu, Michelle S. Hirsch, Karsten Gravdal, Sangeetha Palakurthi, Diane R. Bielenberg, Lars A. Akslen, Ronny Drapkin, Vivek Mittal, Randolph S. Watnick

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The vast majority of ovarian cancer-related deaths are caused by metastatic dissemination of tumor cells, resulting in subsequent organ failure. However, despite our increased understanding of the physiological processes involved in tumor metastasis, there are no clinically approved drugs that have made a major impact in increasing the overall survival of patients with advanced, metastatic ovarian cancer. We identified prosaposin (psap) as a potent inhibitor of tumor metastasis, which acts via stimulation of p53 and the antitumorigenic protein thrombospondin-1 (TSP-1) in bone marrow-derived cells that are recruited to metastatic sites. We report that more than 97% of human serous ovarian tumors tested express CD36, the receptor that mediates the proapoptotic activity of TSP-1. Accordingly, we sought to determine whether a peptide derived from psap would be effective in treating this form of ovarian cancer. To that end, we developed a cyclic peptide with drug-like properties derived from the active sequence in psap. The cyclic psap peptide promoted tumor regression in a patient-derived tumor xenograft model of metastatic ovarian cancer. Thus, we hypothesize that a therapeutic agent based on this psap peptide would have efficacy in treating patients with metastatic ovarian cancer.

Original languageEnglish (US)
Article number329ra34
JournalScience translational medicine
Volume8
Issue number329
DOIs
StatePublished - Mar 9 2016

ASJC Scopus subject areas

  • Medicine(all)

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