COX and cancer

Abstract

The willow tree has been a source of remedies against fever and inflammation since ancient times. Just over a century ago, Hoffman isolated and modified an active compound from the willow tree and offered it for sale as aspirin. Subsequently, a number of similar compounds have been derived, and these have been classified as non-steroidal anti-inflammatory drugs or NSAIDs. These drugs inhibit the enzyme cyclo-oxygenase (COX), which catalyses the conversion of arachidonic acid to prostaglandins (PGs). PGs are important mediators of signal transduction pathways, and are involved in cellular adhesion, growth and differentiation. Aspirin and other NSAIDs are extensively used in cancer patients, primarily for analgesia. However, since the late 1970s, researchers have been interested in whether regular ingestion of aspirin and other NSAIDs can decrease cancer risk. The most persuasive evidence to date relates to colorectal cancer. Is there a role for these drugs in the primary prevention of cancer, or even the treatment of established disease? Here, we review the theoretical, experimental, epidemiological and clinical data relevant to this question. Two isoforms of COX exist, with distinct tissue distributions and physiological functions. COX-1 is constitutively expressed in many tissues and cell types, whereas the inducible isoenzyme COX-2 is pro-inflammatory in nature, and expressed only in response to certain stimuli such as mitogens, cytokines and growth factors. NSAIDs may achieve different degrees of inhibition of COX-1 and COX-2. Specific COX-2 inhibitors such as celecoxib and rofecoxib have been developed, and these largely avoid the gastrointestinal side-effects associated with NSAID use, which are thought to be due mainly to COX-1 inhibition. A number of studies have demonstrated over-expression of COX-2 in solid malignancies including colon,1 prostate,2 and breast3, as well as pancreas, non-small-cell lung, bladder, endometrium and skin basal and squamous cell.4 A significant relation … Address correspondence to Professor J. Waxman, Department of Cancer Medicine, Faculty of Medicine, Imperial College of Science, Technology & Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN. email: j.waxman{at}ic.ac.uk