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

Research output: Contribution to journalArticle

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

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

PMID: 26962158

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Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. / Wang, Suming; Blois, Anna; El Rayes, Tina; Liu, Joyce F.; Hirsch, Michelle S.; Gravdal, Karsten; Palakurthi, Sangeetha; Bielenberg, Diane R.; Akslen, Lars A.; Drapkin, Ronny; Mittal, Vivek; Watnick, Randolph S.

In: Science Translational Medicine, Vol. 8, No. 329, 329ra34, 09.03.2016.

Research output: Contribution to journalArticle

Harvard

Wang, S, Blois, A, El Rayes, T, Liu, JF, Hirsch, MS, Gravdal, K, Palakurthi, S, Bielenberg, DR, Akslen, LA, Drapkin, R, Mittal, V & Watnick, RS 2016, 'Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment' Science Translational Medicine, vol. 8, no. 329, 329ra34. https://doi.org/10.1126/scitranslmed.aad5653

APA

Wang, S., Blois, A., El Rayes, T., Liu, J. F., Hirsch, M. S., Gravdal, K., ... Watnick, R. S. (2016). Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. Science Translational Medicine, 8(329), [329ra34]. https://doi.org/10.1126/scitranslmed.aad5653

Vancouver

Wang S, Blois A, El Rayes T, Liu JF, Hirsch MS, Gravdal K et al. Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. Science Translational Medicine. 2016 Mar 9;8(329). 329ra34. https://doi.org/10.1126/scitranslmed.aad5653

Author

Wang, Suming ; Blois, Anna ; El Rayes, Tina ; Liu, Joyce F. ; Hirsch, Michelle S. ; Gravdal, Karsten ; Palakurthi, Sangeetha ; Bielenberg, Diane R. ; Akslen, Lars A. ; Drapkin, Ronny ; Mittal, Vivek ; Watnick, Randolph S. / Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. In: Science Translational Medicine. 2016 ; Vol. 8, No. 329.

BibTeX

@article{6f2f2217ffa2429d81fca823e9dfa1d4,
title = "Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment",
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.",
author = "Suming Wang and Anna Blois and {El Rayes}, Tina and Liu, {Joyce F.} and Hirsch, {Michelle S.} and Karsten Gravdal and Sangeetha Palakurthi and Bielenberg, {Diane R.} and Akslen, {Lars A.} and Ronny Drapkin and Vivek Mittal and Watnick, {Randolph S.}",
year = "2016",
month = "3",
day = "9",
doi = "10.1126/scitranslmed.aad5653",
language = "English (US)",
volume = "8",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "329",

}

RIS

TY - JOUR

T1 - Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment

AU - Wang, Suming

AU - Blois, Anna

AU - El Rayes, Tina

AU - Liu, Joyce F.

AU - Hirsch, Michelle S.

AU - Gravdal, Karsten

AU - Palakurthi, Sangeetha

AU - Bielenberg, Diane R.

AU - Akslen, Lars A.

AU - Drapkin, Ronny

AU - Mittal, Vivek

AU - Watnick, Randolph S.

PY - 2016/3/9

Y1 - 2016/3/9

N2 - 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.

AB - 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.

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U2 - 10.1126/scitranslmed.aad5653

DO - 10.1126/scitranslmed.aad5653

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JO - Science Translational Medicine

T2 - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

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