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ABC transporters and their role in nucleoside and nucleotide drug resistance

Yu Fukuda1, John D Schuetz

  • 1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Yu.Fukuda@stjude.org

Biochemical Pharmacology
|January 31, 2012
PubMed

Insights

ATP-binding cassette (ABC) transporters contribute to drug resistance against nucleoside-based chemotherapy. Recent studies show ABCC and ABCG2 transporters reduce intracellular drug concentrations, impacting treatment efficacy.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • ATP-binding cassette (ABC) transporters are critical in multidrug resistance.
  • Nucleoside-based drugs are widely used for malignancies and viral diseases.
  • The role of ABC transporters in nucleoside drug resistance is a recent discovery.

Purpose of the Study:

  • To review the role of ABC transporters in nucleoside drug resistance.
  • To discuss the mechanisms by which ABC transporters affect nucleoside drug efficacy.
  • To highlight the interaction between ABC transporters and nucleoside drug metabolism.

Main Methods:

  • Literature review of studies on ABC transporters and nucleoside drugs.
  • Analysis of mechanisms of nucleoside drug uptake, activation, and efflux.
  • Examination of specific ABC transporter family members (ABCC, ABCG2) involved in resistance.

Main Results:

  • ABC transporters, particularly ABCC subfamily members and ABCG2, actively efflux monophosphorylated nucleoside drugs.
  • This efflux reduces intracellular drug concentrations, contributing to treatment failure.
  • Defects in nucleoside uptake or kinase activation are not the sole mechanisms of resistance.

Conclusions:

  • ABC transporters play a significant role in nucleoside drug resistance, challenging previous assumptions.
  • Understanding ABC transporter interactions is crucial for improving nucleoside-based cancer therapies.
  • Targeting ABC transporters may offer new strategies to overcome drug resistance.

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