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[Drug resistance mediated by ABC transporters]

Megumi Yoshikawa1, Akiko Ito, Toshihisa Ishikawa

  • 1Dept. of Drug Metabolism and Disposition, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan.

Gan to Kagaku Ryoho. Cancer & Chemotherapy
|January 31, 2004
PubMed

Insights

Multidrug resistance in cancer, driven by ATP-binding cassette (ABC) transporters, hinders chemotherapy. Understanding genetic variations in these transporters is key for personalized cancer medicine.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Oncology

Background:

  • Multidrug resistance (MDR) in cancer chemotherapy is a significant clinical challenge, limiting treatment efficacy.
  • ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp), MRP1, and ABCG2/BCRP, actively efflux chemotherapeutic drugs from cancer cells, causing MDR.
  • These transporters are also present in normal tissues, influencing drug pharmacokinetics and the disposition of endogenous and exogenous substances.

Purpose of the Study:

  • To review the role of ABC transporters in cancer multidrug resistance.
  • To highlight the significance of genetic polymorphisms in ABC transporter genes.
  • To emphasize the potential of pharmacogenomic analysis for developing personalized cancer therapies.

Main Methods:

  • Literature review of studies on ABC transporters in cancer and their association with drug resistance.
  • Analysis of research on the functional impact of single nucleotide polymorphisms (SNPs) in ABC transporter genes.
  • Discussion of the implications of ABC transporter genetic variations for drug response and personalized medicine.

Main Results:

  • ABC transporters are critical mediators of MDR by actively exporting anticancer drugs.
  • Specific ABC transporters like P-gp, MRP1, and ABCG2/BCRP are well-characterized for their role in drug efflux.
  • Numerous SNPs have been identified within ABC transporter genes, suggesting a genetic basis for inter-individual variability in drug response.

Conclusions:

  • ABC transporters significantly impact drug pharmacokinetics and are major contributors to chemotherapy resistance.
  • Genetic polymorphisms in ABC transporters offer insights into individual differences in drug response.
  • Functional analysis of these polymorphisms is crucial for advancing personalized medicine strategies in oncology.

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