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Drug Resist Updat. 1999 Dec;2(6):351-357.

Molecular mechanisms of resistance to taxanes and therapeutic implications.

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Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, 20133, Italy


The mechanism of resistance to taxanes has not been fully elucidated. Since Taxol is a substrate for P-glycoprotein, overexpression of this transport system is recognized as a relevant mechanism of resistance. Additional mechanisms include changes of microtubule structure and/or composition resulting in reduced drug binding to the target. Current efforts are directed at clarifying the role of cellular response to drug-induced damage to cytoskeleton and mitotic spindle. Downstream events, such as control of cell cycle progression and regulation of cell death pathways, are likely to play a relevant role in cellular sensitivity to antimicrotubule agents. The identification of resistance factors and critical determinants of antitumor efficacy of microtubule-stabilizing agents is essential to (i) improve their therapeutic efficacy; and (ii) to design non-cross-resistant compounds. The present review discusses the possible therapeutic implications of the recent progress in the field of resistance to taxanes.


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