Cyclooxygenases in cancer: progress and perspective

Cancer Letters
Shan ZhaAngelo M De Marzo

Abstract

Aspirin has been used to control pain and inflammation for over a century. Epidemiological studies first associated a decreased incidence of colorectal cancer with the long-term use of aspirin in the early 1980s. Near the same time the first reports showing regression of colorectal adenomas in response to the non-steroidal anti-inflammatory drug (NSAID) sulindac were reported. In subsequent years, the use of other NSAIDs, which inhibit cyclooxygenase (COX) enzymes, was linked to reduced cancer risk in multiple tissues including those of the breast, prostate, and lung. Together these studies resulted in the identification of a new cancer preventive and/or therapeutic target-COX enzymes, especially COX-2. Meanwhile, the overexpression of COX-2, and less consistently, the upstream and downstream enzymes of the prostaglandin synthesis pathway, was demonstrated in multiple cancer types and some pre-neoplastic lesions. Direct interactions of prostaglandins with their receptors through autocrine or paracrine pathways to enhance cellular survival or stimulate angiogenesis have been proposed as the molecular mechanisms underlying the pro-carcinogenic functions of COX-2. The rapid development of safe and effective inhibitors targeting in...Continue Reading

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