Celecoxib with chemotherapy in colorectal cancer.
Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response. Many primary and metastatic cancers express COX-2, and its presence is correlated with tumor angiogenesis, more invasive tumor phenotype, resistance to apoptosis, and systemic immunosuppression. The expression of COX-2 is associated with a worse prognosis. Inhibition of prostaglandin synthesis may be beneficial in human malignancy. Regular consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of, and mortality rate resulting from, a number of types of gastrointestinal cancers. Premalignant colonic lesions regress following the administration of nonspecific COX inhibitors, such as sulindac (Clinoril). Advanced solid tumor patients treated with indomethacin (Indocin) survive twice as long as do such patients who receive supportive care alone. The U.S. Food and Drug Administration has approved specific COX-2 inhibitors for the treatment of arthritis, pain, and familial adenomatous polyposis. Preclinical studies show that these drugs block angiogenesis, suppress solid tumor metastases, and slow the growth of implanted gastrointestinal cancer cell lines. The COX-2 inhibitors have safely and effectively been combined with chemotherapeutic agents in experimental studies. Ongoing clinical trials are currently assessing the potential therapeutic role of COX-2 inhibitors in both prevention and treatment of a diverse range of human cancers.
Blanke
Charles D
CD
Oregon Health Sciences University, Portland 97201, USA.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D013449:Sulfonamides / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib