Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer.
Cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including oral leukoplakia and squamous cell carcinoma of the head and neck. Increased levels of COX-2 may contribute to carcinogenesis by modulating xenobiotic metabolism, apoptosis, immune surveillance, and angiogenesis. In experimental models, newly developed selective COX-2 inhibitors suppress the formation of tumors, including tongue cancer. These findings provided a rationale for a number of chemoprevention trials that are underway. Selective COX-2 inhibitors also suppress the growth and metastases of established tumors and enhance the anticancer activity of both radiotherapy and chemotherapy in experimental animals. In this review, evidence is presented that inhibition of COX-2 represents a promising strategy to prevent or possibly treat human head and neck cancers.
Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
Derrick T
DT
Lin
Kotha
K
Subbaramaiah
Jatin P
JP
Shah
Andrew J
AJ
Dannenberg
Jay O
JO
Boyle
D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013449:Sulfonamides / Q000627:therapeutic use; D015854:Up-Regulation / Q000502:physiology; D015262:Xenobiotics / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D015262:Xenobiotics; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide