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Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer

Szabolcs Modok1, Howard R Mellor, Richard Callaghan

  • 1Oxford Drug Resistance Group, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.

Current Opinion in Pharmacology
|May 13, 2006
PubMed

Insights

Multidrug resistance transporters like P-glycoprotein reduce chemotherapy effectiveness by pumping drugs out of cancer cells. Research explores their role in chemoresistance and potential drugs to overcome it.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer cells exhibit resistance to anticancer agents, a phenomenon recognized early in research.
  • Reduced drug accumulation was identified as a key factor in cancer cell resistance in 1973.
  • The discovery of P-glycoprotein mediating drug efflux by Juliano and Ling in 1973 marked a significant advancement.

Purpose of the Study:

  • To review the contribution of multidrug resistance transporters to cancer chemoresistance.
  • To assess the clinical utility of drugs designed to sensitize cancers to chemotherapy.
  • To evaluate the progress in understanding drug efflux mechanisms in cancer cells over three decades.

Main Methods:

  • Literature review of early publications and seminal findings on drug resistance.
  • Examination of the discovery and characterization of key multidrug resistance transporters.
  • Analysis of research advancements in understanding transporter-mediated drug efflux.

Main Results:

  • P-glycoprotein (MDR1, ABCB1) was identified as a major mediator of drug efflux.
  • Other ATP-binding cassette (ABC) transporters, including MRP1 (ABCC1) and BCRP (ABCG2), were discovered in various cancers.
  • Despite extensive research, the precise contribution of these transporters to clinical chemoresistance remains a subject of investigation.

Conclusions:

  • Multidrug resistance transporters play a significant role in cancer chemoresistance.
  • The development of clinically effective drugs to overcome transporter-mediated resistance is ongoing.
  • Further research is needed to fully define the therapeutic potential of targeting these transporters.

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