Optimized NSAIDs for Breast Cancer Prevention
Abstract
Population studies have shown that women who use non-steroidal anti-inflammatory drugs (NSAIDs) developbreast 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 breastcancer is not understood. This project will develop an optimized NSAID for breast cancer prevention that can betaken safely at high doses, and will determine its mechanisms of action. The side effects of NSAlDs are mainly dueto inhibition of cyclo-oxygenase (COX) enzymes. Based on preliminary experiments, we hypothesize that thepreventative action of NSAlDs in breast cancer is not solely due to COX inhibition, but rather to alterations of otherbiochemical pathways in breast cells that control their proliferation. We have isolated modified NSAIDs that do notinhibit the COX enzyme, but still retain chemopreventative activity. Testing this COX independent NSAlD in arobust model of breast cancer, the MMTV-wnt1 transgenic mouse, has revealed a trend towards tumor preventionand a significant reduction in gene expression of wnt regulated targets. These data have already encouragedearly, biomarker based, clinical trials in women with breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA455338
Entities
People
- Dennis A. Carson
Organizations
- University of California, San Diego