Guanylyl cyclase C (GCC), which is expressed in intestinal epithelial cells and colorectal tumors, may represent a therapeutic target for metastatic colon cancer, according to the results of a study in mice published in the July 2 issue of the Journal of the National Cancer Institute.

Adam E. Snook, of Thomas Jefferson University in Philadelphia, and colleagues immunized BALB/c mice with viral vectors expressing GCC before or after administration of GCC-expressing mouse colon cancer cells.

The investigators found that immunization with GCC-expressing vectors reduced formation of liver metastases compared to controls (3.55 nodules versus 30.4 nodules, respectively) and lung metastases (55.7 versus 263 nodules, respectively). Therapeutic immunization was associated with a longer survival time in mice carrying lung metastases (38 days versus 29 days compared to controls), without autoimmunity.

"These observations establish a framework for exploiting immunologic compartmentalization beyond the gastrointestinal tract to achieve antimetastatic therapy in tumors that originate from other mucosae, including oral, respiratory, mammary and urogenital for the treatment of cancers of the head and neck, lung, breast, vagina and bladder, respectively," the authors write.

Two co-authors disclosed relationships with Amgen, Inc., Merck Research Laboratories, and Targeted Diagnostics and Therapeutics, Inc., the latter of which provided funding for the study.

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