Cyclooxygenase-2 as a target for prevention of colorectal cancer.

COX-2 is an isoenzyme of cyclooxygenase that is increased in response to growth factors, cytokines, and other mitogenic stimuli. Upregulation of COX-2 gene expression and functional activity is an early event in colorectal tumor formation. The long-term use of cyclooxygenase inhibitors, such as aspirin and nonsteroidal anti-inflammatory drugs, is associated with a decreased rate of colorectal tumors. This observation holds across a range of experimental models, from animal genetic tumor models to large epidemiologic studies of human sporadic colorectal cancer. Selective inhibitors of COX-2 were primarily developed to treat COX-2-related inflammation with minimal side effects. These drugs, however, may also provide safe, effective chemoprevention of colorectal neoplasia.