Authors: Louise R. Howe (Weill Medical College of Cornell University and Strang Cancer Research Laboratory, New York, NY )
Abstract: The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is currently the focus of considerable interest as a potential anti-cancer target. COX-2 is normally expressed predominantly in kidney and brain, and has important roles in reproduction and inflammation, but recently COX-2 misexpression has been reported in numerous human cancers. COX-2 is overexpressed in about 40% of invasive breast carcinomas and at a higher frequency in ductal carcinoma in situ. Several studies have identified correlations between COX-2 expression and poor patient prognosis, HER2/neu overexpression and negative hormone receptor status. Animal studies using transgenic overexpression and knockout approaches to manipulate Cox-2 gene dosage have confirmed an important role for Cox-2 in tumorigenesis. Furthermore, preclinical experiments using rodent breast cancer models suggest COX-2 inhibition to be an effective strategy for both prevention and treatment of experimental breast cancer. Since COX-2 can contribute to multiple facets of tumorigenesis, including angiogenesis, several mechanisms are likely to underlie the anti-cancer action of COX inhibitors. The emerging relationship between the estrogen synthase aromatase and COX suggests that aromatase suppression may be an important breast-specific component of COX inhibitor-mediated chemoprevention. Selective COX-2 inhibitors may also be useful in combination with established therapeutic approaches to enhance their efficacy and ameliorate side effects. Thus, selective COX-2 inhibitors offer considerable promise for the prevention and treatment of human breast cancer.