Taxol: mechanisms of action and resistance

J Natl Cancer Inst Monogr. 1993;(15):55-61.

Abstract

Information on the mechanisms of action and of resistance to Taxol, as well as new data from our laboratory on the promoter regions of the genes that encode P-glycoprotein in a murine Taxol-resistant cell line, is discussed. Taxol induces the formation of stable bundles of microtubules, thereby interfering with the normal function of cellular microtubules. The drug can induce the multidrug-resistance (MDR) phenotype that includes the overproduction of P-glycoprotein, a membrane glycoprotein that acts as a drug efflux pump. In human tumors resistant to Taxol, P-glycoprotein could be responsible for maintaining the drug below cytotoxic levels. Analyses of the MDR promoters that are involved in P-glycoprotein expression and overproduction revealed an interesting recombination event in a Taxol-resistant cell line. As an important new clinical agent for the treatment of malignancies, Taxol requires further mechanistic investigations at the preclinical level.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Carrier Proteins / genetics
  • Drug Resistance / genetics
  • Humans
  • Membrane Glycoproteins / genetics
  • Paclitaxel / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carrier Proteins
  • Membrane Glycoproteins
  • Paclitaxel