GUCY2C ligand replacement to prevent colorectal cancer

Despite advances in screening and prevention strategies, colorectal cancer (CRC) remains the second-leading cause of cancer-related death in the United States. Given this continued public health burden of CRC, there is a clear need for improved disease prevention. CRC initiates and progresses over d...

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Bibliographic Details
Published in:Cancer biology & therapy 2016-07, Vol.17 (7), p.713-718
Main Authors: Blomain, Erik S., Pattison, Amanda M., Waldman, Scott A.
Format: Article
Language:English
Subjects:
Chemoprevention
colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - pathology
Colorectal Neoplasms - prevention & control
guanylin
guanylyl cyclase C
Humans
Ligands
linaclotide
Receptors, Enterotoxin
Receptors, Guanylate Cyclase-Coupled - genetics
Receptors, Peptide
Review
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Summary:Despite advances in screening and prevention strategies, colorectal cancer (CRC) remains the second-leading cause of cancer-related death in the United States. Given this continued public health burden of CRC, there is a clear need for improved disease prevention. CRC initiates and progresses over decades, canonically proceeding via a series of stepwise molecular events that turn a normal epithelium into a dysfunctional epithelium, then subsequently into an adenoma, and finally an invasive adenocarcinoma. An emerging paradigm suggests that guanylyl cyclase C (GUCY2C) functions as a tumor suppressor in the intestine, and that the loss of hormone ligands for this receptor causes epithelial dysfunction and represents an important step in the disease process. In that context, GUCY2C ligand replacement therapy has been proposed as a strategy to prevent colorectal cancer, a translational opportunity that is underscored by the recent regulatory approval of the oral GUCY2C ligand linaclotide (Linzess™, Forest Laboratories and Ironwood Pharmaceuticals, Inc.).
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2016.1178429