THE TRANSPORT AND BINDING OF TAXOL

1. This review brings together the information available to date regar ding how taxol cytotoxicity and the development of resistance to this drug is affected by its cellular transport and intra cellular binding. 2. Taxol, a potent anticancer drug first extracted from the bark of t he Pacific yew tree, is extremely effective in the treatment of a wide range of malignancies. 3. Unlike other antimitotic drugs, taxol promo tes the formation of highly stable microtubules that resist depolymeri zation by specifically binding to the N-terminal region of beta-tubuli n. Taxol binding alters the conformation of the tubulin subunit, thus greatly retarding tubulin heterodimer dissociation. 4. Cell division i s then blocked at the mitotic stage and the cell dies. 5. Besides this central mechanism, taxol exerts numerous other cellular effects. 6. O bservations made with taxol resistant murine and human: tumor cells ma ke it increasingly clear that the cellular transport of taxol and its microtubule binding activity are important factors in the development of resistance to this drug. GEN PHARMAC 29;2:167-172, 1997. (C) 1997 E lsevier Science Inc.