Cardiovascular risk markers and mechanisms in targeting the COX pathway for colorectal cancer prevention.

COX-2 inhibition reduces the incidence of colorectal neoplasia. The increased risk of thrombotic cardiovascular events produced by selective or nonselective COX-2 inhibitors, however, has confounded the consideration of employing them in cancer prevention. Developing a strategy for preventing colorectal cancer by inhibiting COX-2 depends on research advances in several key areas, including predictive biomarkers to identify people at the lowest risk for cardiovascular events, the molecular mechanisms whereby interdicting the COX-2 pathway produces thrombotic events, and the pharmacology of the widely divergent agents that act on COX-2 and its downstream pathway.