A role for cyclooxygenase-2 inhibitors in the prevention and treatment of cancer.

Cyclooxygenase-2 (COX-2) is being intensively evaluated as a pharmacologic target for both the prevention and treatment of cancer. Aberrant COX-2 expression was initially described in colorectal cancers and has now been detected in many human tumors, including breast cancers. Strikingly, forced expression of COX-2 in murine mammary gland drives tumor formation. Moreover, knocking out COX-2 protects against the formation of intestinal and skin tumors in animal cancer models. Consistent with these findings, selective COX-2 inhibitors possess anticancer properties. For example, selective COX-2 inhibitors reduce the formation and growth of experimental breast and colon cancers. Importantly, selective COX-2 inhibitors do not inhibit platelet function and cause fewer gastrointestinal side effects (peptic ulcer disease) than traditional nonsteroidal anti-inflammatory drugs. Clinical trials are warranted to define the role of selective COX-2 inhibitors in the prevention and treatment of cancer.