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Mechanisms of multidrug resistance: the potential role of microtubule-stabilizing agents

T Fojo1, M Menefee

  • 1National Cancer Institute, Bethesda, MD 20892, USA. tfojo@helix.nih.gov

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|October 13, 2007
PubMed

Insights

Novel microtubule-stabilizing agents, including epothilones, show promise against solid tumors. These agents may overcome drug resistance, offering new chemotherapy options for patients with taxane-resistant cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Antimitotic agents targeting microtubule dynamics are crucial in chemotherapy for solid tumors.
  • Taxanes (paclitaxel, docetaxel) are widely used but face drug resistance issues.
  • Epothilones offer superior potency and activity against taxane-resistant tumors, unaffected by P-glycoprotein efflux.

Purpose of the Study:

  • To review mechanisms of drug resistance to antimitotic agents.
  • To summarize data on novel microtubule-stabilizing agents, focusing on epothilones.
  • To evaluate the potential of these agents in overcoming drug resistance and expanding treatment options.

Main Methods:

  • Literature review of scientific and clinical data on microtubule-stabilizing agents.
  • Comparison of epothilones with taxanes regarding efficacy, resistance mechanisms, and pharmacologic profiles.
  • Analysis of in vitro and preclinical model data for novel agents.

Main Results:

  • Epothilones demonstrate superior potency and activity against taxane-resistant tumors compared to taxanes.
  • Epothilones are not susceptible to P-glycoprotein-mediated drug efflux, a common resistance mechanism.
  • Other natural-product microtubule-stabilizing agents also exhibit promising pharmacological properties.

Conclusions:

  • Novel microtubule-stabilizing agents, particularly epothilones, hold significant potential for broad antitumor efficacy.
  • These agents may circumvent common drug resistance mechanisms, including those affecting taxanes.
  • The development of resistance-resilient microtubule agents offers valuable new therapeutic strategies for cancer treatment.

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