Molecular mechanisms of resistance to taxanes and therapeutic implications

Franco Zunino, Giuliana Cassinelli, Donatella Polizzi, Paola Perego

Research output: Contribution to journalArticle

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. (C) 1999 Harcourt Publishers Ltd.

Original languageEnglish
Pages (from-to)351-357
Number of pages7
JournalDrug Resistance Updates
Volume2
Issue number6
DOIs
Publication statusPublished - Dec 1999

ASJC Scopus subject areas

  • Cancer Research
  • Infectious Diseases
  • Oncology
  • Pharmaceutical Science

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