Guanylyl cyclase C (GUCY2C/GCC) is a member of the receptor guanylyl cyclase family. This enzyme serves as the intestinal receptor for the heat-stable enterotoxin produced by bacteria, hence known as the heat-stable enterotoxin receptor. It encodes a type I transmembrane protein with a molecular weight of approximately 120 kDa. Research indicates that activation of guanylyl cyclase C stimulates the production of the second messenger cyclic guanosine monophosphate (cGMP) intracellularly, playing roles in regulating homeostasis, maintaining intestinal barrier function, and exerting anti-inflammatory effects.
Recent studies have found stable expression of GUCY2C in primary colorectal cancer cells, while metastatic colorectal cancer cells exhibit abnormally high GUCY2C expression, suggesting it may serve as a specific marker for metastatic colorectal cancer. Data also suggest the expression of GUCY2C in pancreatic, gastric, and esophageal cancers, indicating its potential as a target for these diseases.
Although there are currently no GUCY2C-targeted drugs on the market, GUCY2C has been studied in immunotherapies such as vaccines, immunotoxins, and CAR-T cells. Clinical research data on Pfizer's GUCY2C-CD3 bispecific antibody PF-0706119 in tumors have shown promising tumor-targeting activity.
