TY - JOUR
T1 - Molecular mechanisms of resistance to taxanes and therapeutic implications
AU - Zunino, Franco
AU - Cassinelli, Giuliana
AU - Polizzi, Donatella
AU - Perego, Paola
PY - 1999/12
Y1 - 1999/12
N2 - 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. (C) 1999 Harcourt Publishers Ltd.
AB - 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. (C) 1999 Harcourt Publishers Ltd.
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U2 - 10.1054/drup.1999.0108
DO - 10.1054/drup.1999.0108
M3 - Article
AN - SCOPUS:0033503104
VL - 2
SP - 351
EP - 357
JO - Drug Resistance Updates
JF - Drug Resistance Updates
SN - 1368-7646
IS - 6
ER -