COX-2 inhibitors for the prevention of breast cancer.
The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is normally expressed predominantly in kidney and brain, and also has important roles in reproduction and inflammation. COX-2 misexpression has been observed in numerous human cancers, including the majority of colorectal cancers. Recently, COX-2 overexpression has been described in human breast cancer. COX-2 is present in about 40% of invasive breast carcinomas, particularly those that overexpress HER2/neu, and COX-2 expression correlates with poor patient prognosis. Manipulation of Cox-2 gene dosage by using transgenic overexpression and knockout approaches has revealed an important role for Cox-2 in tumorigenesis. Furthermore, translational experiments using rodent breast cancer models suggest COX-2 inhibition to be an effective strategy for both prevention and treatment of experimental breast cancers. Since COX-2 can contribute to multiple facets of tumorigenesis, including angiogenesis, several mechanisms are likely to underlie the anticancer action of COX inhibitors. Thus, selective COX-2 inhibitors offer considerable promise for the prevention and treatment of human breast cancer.
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York, USA. lrhowe@med.cornell.edu
Louise R
LR
Howe
Andrew J
AJ
Dannenberg
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009153:Mutagens; D009389:Neovascularization, Pathologic; D011247:Pregnancy; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D019076:Transgenes; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009153:Mutagens; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases