Optimized NSAIDS for Breast Cancer Prevention.

摘要

Population studies have shown that women who use non-steroidal anti- inflammatory drugs (NSAIDs) develop breast cancer less frequently. However, these drugs have side effects toward the stomach, liver and kidneys, particularly at the high doses potentially required to prevent breast cancer. Also, how these agents prevent breast cancer is not understood. This project will develop an optimized NSAID for breast cancer prevention that can be taken safely at high doses, and will determine its mechanisms of action. The side effects of NSAIDs are mainly due to inhibition of the cyclo-oxygenase (COX) enzyme. Eased on preliminary experiments, we hypothesize that the preventative action of NSAlDs in breast cancer is not due to COX inhibition, but rather to alterations of other biochemical pathways in breast cells that control their proliferation. We have isolated modified NSAIDs that do not inhibit COX inhibitors, but still retain chemopreventative activity. We will study genetically modified mice that frequently develop breast cancer. The mice will be fed diets supplemented with placebo or with the modified NSAID that does not inhibit COX. We shall determine if the new agent prevents breast cancer without toxicity to normal cells, and will measure biochemical parameters associated with its proposed mechanisms of action.