The role of topical cyclo-oxygenase-2 inhibitors in skin cancer: treatment and prevention.

Cyclo-oxygenases (COXs) are rate-limiting enzymes in arachidonic acid metabolism and prostaglandin production. COX-2 is the main UV-responsive COX isoform in human skin and is involved in UV-induced skin inflammation and apoptosis. The topical NSAID diclofenac works as a nonspecific COX inhibitor and is an effective and well tolerated treatment for actinic keratosis, which is a principal precursor of cutaneous squamous cell carcinoma. Oral and topical COX-2 inhibitors have chemopreventive activity against chemically and UV light-induced skin cancer in animal models. The mechanism of action of COX inhibitors in skin tumorigenesis is complex and not completely understood. Clinical trials to evaluate whether topical administration of NSAIDs or specific COX-2 inhibitors can prevent skin cancer in high-risk patients are warranted.