Subbaramaiah Kotha, Dannenberg Andrew J
Weill Medical College of Cornell University, Dept of Medicine, New York, NY 10021, USA.
Trends Pharmacol Sci. 2003 Feb;24(2):96-102. doi: 10.1016/S0165-6147(02)00043-3.
Cyclooxygenase2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers. Here, the potential utility of selective COX-2 inhibitors in the prevention and treatment of cancer is considered. The mechanisms by which COX-2 levels increase in cancers, key data that indicate a causal link between increased COX-2 activity and tumorigenesis, and possible mechanisms of action of COX-2 are discussed. In a proof-of-principle clinical trial, treatment with the selective COX-2 inhibitor celecoxib reduced the number of colorectal polyps in patients with familial adenomatous polyposis. Selective COX-2 inhibitors appear to be sufficiently safe to permit large-scale clinical testing and numerous clinical trials are currently under way to determine whether selective inhibitors of COX-2 are effective in the prevention and treatment of cancer.
环氧化酶2(COX-2)是一种诱导性前列腺素G/H合酶,在多种人类癌症中过度表达。本文探讨了选择性COX-2抑制剂在癌症预防和治疗中的潜在应用价值。讨论了癌症中COX-2水平升高的机制、表明COX-2活性增加与肿瘤发生之间存在因果关系的关键数据,以及COX-2可能的作用机制。在一项原理验证临床试验中,选择性COX-2抑制剂塞来昔布治疗可减少家族性腺瘤性息肉病患者的结直肠息肉数量。选择性COX-2抑制剂似乎足够安全,可以进行大规模临床试验,目前正在进行多项临床试验,以确定COX-2选择性抑制剂在癌症预防和治疗中是否有效。