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ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development

Young Hee Choi, Ai-Ming Yu1

  • 1Biochemistry & Molecular Medicine, UC Davis Medical Center, 2700 Stockton Blvd., Suite 2132, Sacramento, CA 95817, USA. aimyu@ucdavis.edu.

Current Pharmaceutical Design
|May 22, 2013
PubMed

Insights

Multidrug resistance (MDR) in cancer is often caused by ATP-binding cassette (ABC) transporters. Developing effective MDR modulators requires reliable preclinical assays to assess drug transport and pharmacokinetics.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Multidrug resistance (MDR) significantly hinders cancer chemotherapy efficacy.
  • Overexpression of ATP-binding cassette (ABC) efflux transporters, including P-glycoprotein (P-gp/ABCB1), MRP1/ABCC1, and BCRP/ABCG2, in cancer cells limits anticancer drug exposure.
  • Current MDR modulators offer limited clinical benefits and can cause toxicity or drug-drug interactions.

Purpose of the Study:

  • To review the role of ABC efflux transporters in MDR and pharmacokinetics.
  • To discuss preclinical assays for evaluating drug transport mediated by ABC transporters.
  • To explore the development of novel MDR modulators.

Main Methods:

  • Literature review of studies on ABC transporters, MDR, and pharmacokinetics.
  • Analysis of preclinical assay methodologies for assessing transporter function.
  • Discussion of challenges and strategies in developing MDR modulators.

Main Results:

  • ABC transporters play a critical role in both cancer MDR and normal physiological drug disposition.
  • Existing chemosensitizers have shown limited success due to toxicity, drug interactions, and overlapping substrate specificities of co-expressed transporters.
  • There is a need for robust preclinical models to predict in vivo transporter effects.

Conclusions:

  • Effective strategies to overcome MDR in cancer require a deeper understanding of ABC transporter function.
  • Reliable preclinical assays are essential for the development of safe and effective MDR modulators and for predicting drug pharmacokinetics.
  • Further research into transporter-mediated drug disposition is crucial for improving cancer pharmacotherapy.

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