TARGETING GUANYLATE CYCLASE C IN COLORECTAL CANCER: WHERE ARE WE NOW?

Colorectal cancer (CRC) is a leading cause of cancer-related death in the world, exceeding 1 million new cases and 700,000 deaths annually. The past decade has witnessed a modest decline in CRC incidence, consistent with screening initiatives and risk factor reduction. While colonoscopy and the removal of precancerous adenomas remains the most effective way to prevent CRC, new paradigms in prevention and treatment are needed. In that context, guanylate cyclase C (GUCY2C) is an emerging target for CRC chemoprevention and immunotherapy. GUCY2C, a transmembrane receptor selectively expressed by intestinal epithelium, regulates key homeostatic mechanisms including proliferation, metabolism and barrier function. GUCY2C expression persists throughout the development of CRC but its function is silenced early in tumorigenesis by the near-universal loss of its endogenous paracrine hormones, guanylin and uroguanylin. Here, we explore therapeutic opportunities in CRC prevention and treatment targeting GUCY2C and its signaling axis.