COX-2 Blockade in Cancer Prevention and Therapy

The revelation that aspirin and aspirin-like compounds have notableantineo­ plastic properties has revolutionized cancer research. COX-2 Blockade in Cancer Prevention and Therapy chronicles the evidence and presents exciting new op­ portunities for the use of cyclooxygenase-2 (COX-2) blockade in the prevention and treatment of cancer. The text is divided broadly into five areas. First, an historical overview documents the scientific discovery ofCOX-2 and the pharma­ ceutical development of nonsteroidal anti-inflammatory drugs (NSAIDs) designed for selective COX-2 inhibition. The process by which essential poly­ unsaturated fatty acids (PUF As) stimulate prostaglandin biosynthesis and cancer development, and its interruption by COX-2 inhibition, is elucidated. This is followed by a section on the epidemiology of NSAIDs and cancers of the colon and breast, and other anatomic sites. These chapters reflect significant cancer protection owing to the regular use of common NSAIDs such as aspirin and ibuprofen. A section on animal models of carcinogenesis presents comprehensive evidence that general NSAIDs inhibit a variety of malignant neoplasms in vivo, and highlights recent findings which show that COX-2 blocking agents produce striking chemopreventive effects against colon cancer and breast cancer as well as other malignancies. Genetic models are presented confirming the critical role of COX-2 in carcinogenesis. Section IV then discusses the molecular biology of COX -2 vis-a-vis the role of COX -2 and, to a lesser extent, COX -1, in modulating a number of important processes in molecular carcinogenesis such as mutagen­ esis, cell division, angiogenesis, cell differentiation, and apoptosis.