Guanylyl cyclase C as a biomarker for targeted imaging and therapy of metastatic colorectal cancer

Abstract

The guanylyl cyclase C (GCC) receptor posseses several well-established properties ideal for use as a biomarker in gastrointestinal malignancies. The GCC receptor is constitutively expressed in the apical membranes of the intestine and its expression is universally preserved in primary colorectal tumors and their metastases. Moreover, receptor binding is retained by GCC’s cognate ligand, the bacterial enterotoxin ST, even after conjugation to functional moieties. Selective tumor, but not gastrointestinal, uptake of ST in mice bearing GCC-expressing colon cancer xenografts demonstrates the potential of exploiting ST–GCC interaction for diagnostic imaging and targeted therapy of metastatic colorectal cancer. We expect this specific targeting provided by ST–GCC interaction to improve diagnosis, staging and management of colorectal cancer metastases, and ultimately prolong patient survival in this disease.