期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 25, 期 5, 页码 335-346出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2021.1937124
关键词
cGMP; gastrointestinal cancers; guanylyl cyclase c; immunotherapy; ligand replacement; phosphodiesterase inhibitors
资金
- National Institutes of Health [R01 CA204881, R01 CA206026, P30 CA56036]
- Defense Congressionally Directed Medical Research Program [W81XWH-17-PRCRPTTSA]
- Targeted Diagnostic & Therapeutics, Inc.
- Defense Congressionally Directed Medical Research Programs [W81XWH-17-1-0299, W81XWH-19-1-0263, W81XWH-19-1-0067]
- Courtney Ann Diacont Memorial Foundation
- PhRMA Foundation
GUCY2C has emerged as a promising target for chemoprevention and therapy for GI malignancies, with potential roles in immunotherapy and diagnostic management as well. Clinical trials are underway to explore its use as an immunotherapeutic target for preventing metastatic disease. GUCY2C is an emerging target across the disease continuum, from chemoprevention to the prevention of metastatic diseases.
Introduction Gastrointestinal (GI) cancers account for the second leading cause of cancer-related deaths in the United States. Guanylyl cyclase C (GUCY2C) is an intestinal signaling system that regulates intestinal fluid and electrolyte secretion as well as intestinal homeostasis. In recent years, it has emerged as a promising target for chemoprevention and therapy for GI malignancies. Areas Covered The loss of GUCY2C signaling early in colorectal tumorigenesis suggests it could have a significant impact on tumor initiation. Recent studies highlight the importance of GUCY2C signaling in preventing colorectal tumorigenesis using agents such as linaclotide, plecanatide, and sildenafil. Furthermore, GUCY2C is a novel target for immunotherapy and a diagnostic marker for primary and metastatic diseases. Expert Opinion There is an unmet need for prevention and therapy in GI cancers. In that context, GUCY2C is a promising target for prevention, although the precise mechanisms by which GUCY2C signaling affects tumorigenesis remain to be defined. Furthermore, clinical trials are exploring its role as an immunotherapeutic target for vaccines to prevent metastatic disease. Indeed, GUCY2C is an emerging target across the disease continuum from chemoprevention, to diagnostic management, through the treatment and prevention of metastatic diseases.
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