Celecoxib: a specific COX-2 inhibitor with anticancer properties.
In addition to the well-established pathophysiological role that COX-2 plays in inflammation, recent evidence implies that this isoform may also be involved in multiple biologic events throughout the tumorigenic process. Many epidemiological studies demonstrate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of a wide range of tumors. Further, COX-2 is chronically overexpressed in many premalignant, malignant, and metastatic human cancers, and levels of overexpression have been shown to significantly correlate to invasiveness, prognosis, and survival in some cancers. Pharmacological studies consistently demonstrate that COX-2 inhibitors dose-dependently inhibit tumor growth and metastasis in various relevant animal models of cancer. Importantly, several investigators have also shown COX-2 inhibitors may act additively or synergistically with currently used cytotoxics and molecularly targeted agents. Here we present a broad overview of the growing evidence that COX-2 plays a pivotal role throughout oncogenesis and summarize the rationale to explore the use of COX-2 inhibitors for the prevention and/or treatment of cancer as a single agent or in combination with current anticancer modalities.
Koki
Alane T
AT
Pharmacia Corporation, Chesterfield, MO 63017, USA. alane.t.koki@pharmacia.com
Masferrer
Jaime L
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C496540:PTGS2 protein, human