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Multidrug resistance.

I Pastan1, M M Gottesman

  • 1Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Annual Review of Medicine
|January 1, 1991
PubMed
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Cancer cells develop resistance to multiple natural product drugs through an energy-dependent drug efflux pump. Targeting this multidrug transporter, encoded by the MDR1 gene, could improve cancer treatment outcomes.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Oncology

Background:

  • Cancer cells can acquire resistance to various chemotherapy drugs.
  • Multidrug resistance (MDR) is a significant challenge in cancer treatment.
  • The MDR1 gene encodes a key protein involved in drug efflux.

Purpose of the Study:

  • To investigate the role of an energy-dependent drug efflux pump in multidrug resistance in cancer cells.
  • To understand the implications of MDR1 gene expression in chemotherapy resistance.
  • To explore strategies for overcoming multidrug resistance in human cancers.

Main Methods:

  • Laboratory investigations of cancer cell lines.
  • Analysis of gene expression, specifically the MDR1 gene.
  • Review of recent clinical studies on multidrug resistance.

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Main Results:

  • Cancer cells express an energy-dependent drug efflux pump, leading to simultaneous resistance to multiple natural product chemotherapeutic drugs.
  • The multidrug transporter, a plasma membrane glycoprotein encoded by the MDR1 gene, is implicated in this resistance.
  • Clinical studies confirm the significant role of this transporter in both intrinsic and acquired chemotherapy resistance across various human cancers.

Conclusions:

  • The MDR1 gene-mediated drug efflux pump is a critical factor in cancer multidrug resistance.
  • Inhibiting this drug efflux pump presents a promising therapeutic strategy for enhancing chemotherapy efficacy.
  • Targeting multidrug resistance mechanisms could significantly impact the treatment of human cancers.