NSAIDs as Cancer Preventive Agents.
Introduction: Targeting of inflammatory states with non-steroidal anti-inflammatory drugs (NSAID'S) is an attractive proposition for cancer prevention. There is abundant epidemiological and experimental evidence that NSAID'S can inhibit tumour development in a number of organs and such drugs have given positive results in human intervention studies. It is hoped that problems with side effects can be overcome by development of specific inhibitors of cancer- and inflammation-associated enzymes. NSAID Pharmacology: Starting with the production of aspirin, NSAIDs have received an enormous amount of clinical attention. Inhibitors of the two isoforms of cyclooxygenase (COX) or prostaglanding G/H synthase, they have found widespread application with increasing interest focused on their employment for cancer prevention. Particular attention is now being drawn to specific inhibitors of the inducible C0X-2 rather than the constitutive COX-1 isoform. Mechanisms of Action: NSAIDs appear to act via depression of prostaglandin synthesis through inhibiting COX-2, often overexpressed in cancers, and the resultant suppression of proliferation, possibly through enhancement of apoptosis. Future Prospectives: The possibility of applying NSAIDs in conjunction with other chemopreventive agents and developing specific inhibitors of different stages in the pathways leading to prostaglandin production and functions hold hope for improved drugs/protocols with reduced detrimental side effects for employment in both primary and secondary cancer prevention in the future.
Wakabayashi
Keiji
K
Division of Prevention, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.