New studies of the relationship between polyunsaturated fatty acid metabolismand carcinogenesis have led to novel molecular targets for cancer chemoprevention research VSports手机版. These targets include procarcinogenic lipoxygenases (LOXs), including 5-, 8-, and 12-LOX, and anticarcinogenic LOXs, including 15-LOX-1 and possibly 15-LOX-2. Recent studies indicate that 15-LOX-1 is down-regulated in colorectal cancer cells and that the ability of nonsteroidal anti-inflammatory drugs, a class of clinically active cancer chemopreventive agents, to induce apoptosis and growth inhibition in these cells was dependent on the induction of 15-LOX-1 and its metabolic product 13-S-hydroxyoctadecadienoic acid. Consistent with the colorectal studies, 15-LOX very recently has shown anticarcinogenic activity in esophageal and prostatic carcinogenesis. Inhibitors of other LOXs (e. g. , 5-LOX) have preclinical anticarcinogenic activity and are being developed for clinical chemoprevention study. These and other LOX data led us to propose that the various LOX pathways exist in a dynamic balance that shifts during carcinogenesis toward 5-, 8-, and 12-LOX (and cyclooxygenase-2) and away from 15-LOX. A novel approach for cancer chemoprevention would involve LOX modulators, i. e. , agents that can induce the anticarcinogenic and/or inhibit the procarcinogenic LOXs, thereby shifting the balance of LOX activities from procarcinogenic to anticarcinogenic metabolism of polyunsaturated fatty acids. .