Estramustine resistance

Estramustine (EM), a conjugate of nornitrogen mustard and estradiol,is a an timicrotubule drug currently in use for the treatment of advanced prostatic carcinoma. Experimental data are accumulating concerning the antitumor eff ect of EM in other malignancies, and clinical studies in other malignancies are ongoing. This review summarizes the information available to date conc erning the effects of EM and the development of drug resistance. EM depolym erizes microtubules by binding to microtubule-associated proteins (MAPs) as well as tubulin. Because of the radiosensitizing effect of this drug there has been a recent increase in interest concerning estramustine and its cli nical use. Recently, it was proposed that EM induces an apoptotic cell deat h in glioma cells in vitro and in a rat model. EM resistance is distinct fr om MDR phenotype; it has been used in combination with antimitotic agents w hich are part of the MDR phenotype. Observations made with estramustine-res istant cell lines show the acquisition of estramustine resistance is a func tion of multiple adaptation by changes at tubulin expression pattern, and i s also associated with changes in tau expression and phosphorylation. (C) 1 999 Elsevier Science Inc. All rights reserved.