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
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