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April 1, 1996The Annual Review of Pharmacology and Toxicology

P-Glycoproteins and Multidrug Resistance

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Authors

WBWilliam BellamyUniversity of Arkansas for Medical Sciences

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Implication

Scientific review reveals P-glycoprotein-mediated efflux drives multidrug resistance in human cancers, indicating pharmacological pump inhibition may restore chemotherapy sensitivity.

Key Points

  • To describe the mechanism of P-glycoprotein-mediated multidrug resistance in neoplastic diseases and assess strategies for reversing resistance using modulating agents.
  • Evaluated preclinical cultured tumor cell lines and clinical human cancer specimens for expression of the MDR1 gene product.
  • Assessed laboratory and clinical data on pharmacological inhibition of P-glycoprotein using adjuvant compounds such as verapamil and cyclosporin.
  • P-glycoprotein functions as an energy-dependent efflux pump that expels cytotoxic natural product drugs from cells, with MDR1 expression correlating with poor clinical prognosis.
  • Co-administration of modulators such as verapamil or cyclosporin with antineoplastic agents diminishes or eliminates drug resistance in laboratory models.
  • P-glycoprotein expression is absent in a subset of drug-resistant tumors, indicating that additional non-P-glycoprotein resistance pathways operate in clinical cancers.

Cite This Study

William Bellamy (1996) studied this question.

synapsesocial.com/papers/6a83253bc91fb0067aa501c2https://doi.org/10.1146/annurev.pa.36.040196.001113
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy.1989 · 561 citations
  2. 2High expression of the multidrug resistance‐associated protein (MRP) in chronic and prolymphocytic leukaemia1994 · 47 citations
  3. 3Expression of a Human Complementary DNA for the Multidrug Resistance Gene in Murine Hematopoietic Precursor Cells With the Use of Retroviral Gene Transfer1990 · 78 citations