title: Molecular mechanisms of resistance to taxanes and therapeutic implications.
abstract: 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. Copyright 1999 Harcourt Publishers Ltd.
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, 20133, Italy
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cassinelli
authors.forename: Donatella
authors.initials: D
authors.lastname: Polizzi
authors.forename: Paola
authors.initials: P
authors.lastname: Perego