Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Feb 6, 2017; 8(1): 47-59
Published online Feb 6, 2017. doi: 10.4292/wjgpt.v8.i1.47
Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice
Wen-Chi L Chang, Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Harry S Cooper, Vaseem A Palejwala, Margie L Clapper, Kunwar Shailubhai
Wen-Chi L Chang, Margie L Clapper, Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA 19111, United States
Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Baruch S. Blumberg Institute, Doylestown, PA 18902, United States
Harry S Cooper, Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, United States
Vaseem A Palejwala, Kunwar Shailubhai, R and D Center, Synergy Pharmaceuticals Inc., Doylestown, PA 18902, United States
Author contributions: Chang WCL, Masih S, Thadi A, Patwa V, Joshi A, Cooper HS, Palejwala VA, Clapper ML and Shailubhai K contributed to study concept, design, data acquisition, analysis and interpretation; Chang WCL, Cooper HS, Palejwala VA, Clapper ML and Shailubhai K contributed to manuscript preparation, critical revision and provided important intellectual content.
Supported by National Cancer Institute (CA133689 to Kunwar Shailubhai, CA006927 to Fox Chase Cancer Center); and an appropriation from the Commonwealth of Pennsylvania (Fox Chase Cancer Center).
Institutional review board statement: Experiments reported in this manuscript did not involve human samples and hence institutional review is not applicable.
Conflict-of-interest statement: Shailubhai K and Palejwala V are employees of Synergy Pharmaceuticals; remaining authors have no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kunwar Shailubhai, Doctor of Philosophy, Chief Scientific Officer, R and D Center, Synergy Pharmaceuticals Inc., 3805 Old Easton Road, Doylestown, PA 18902, United States. shailu@synergypharma.com
Telephone: +1-215-5896308 Fax: +1-215-5896309
Received: June 21, 2016
Peer-review started: June 24, 2016
First decision: August 11, 2016
Revised: September 5, 2016
Accepted: October 25, 2016
Article in press: October 27, 2016
Published online: February 6, 2017
Core Tip

Core tip: Plecanatide, an analog of human uroguanylin, binds and activates guanylate cyclase-C signaling to produce its anti-tumorigenic activity. This study provides the first evidence that oral treatment with plecanatide inhibits inflammation-driven colorectal carcinogenesis. The potential mechanism in Apc+/MinFCCC mice appears to be agonist-mediated activation of guanylate cyclase-C signaling, resulting in inhibition of Wnt/β-catenin pathway and downregulation of pro-inflammatory cytokines and growth factors.