Circumvention of Taxol-Resistance in Human Breast Cancers by Improved Water Soluble Taxanes
Final rept. 1 Sep 2000-1 Sep 2001
PACIFIC MEDICAL CENTER SAN FRANCISCO CA
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The central objective of this investigation was to synthesize and test a novel class of water soluble taxol analogs for potential application in breast cancer chemotherapy, with particular emphasis on overcoming the problem of taxol-resistance that frequently encountered in clinical therapy. We hypothesized that the proposed novel taxol analogs containing both effective functional groups at side chain and strong water soluble moieties at C7 position should be able to circumvent P-glycoprotein mediated multidrug resistance and to enhance the effectiveness in killing taxol-resistant breast cancer cells. We have made significant progress in this research project. Three key intermediate compounds have been successfully synthesized and identified, whereas the synthesis of the proposed taxol analogs is nearing completion. The final intermediate compound has also been made and detected. The feasible and practicable synthetic routes have been established in this project for preparation of these extremely important intermediate compounds that will essentially be used for the successful synthesis of the proposed water soluble taxanes. All these encouraging results will greatly contribute to the development of water soluble taxol analogs for overcoming taxol-resistance in human breast cancers. If this project is successful, the clinical benefits to breast cancer patients could be enormous.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research