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.
Howe
Louise R
LR
Departments of Cell & Developmental Biology and Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Dannenberg
Andrew J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012377:Rodentia
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases