Drug transport by breast cancer resistance protein

Expert Opin Drug Metab Toxicol. 2010 Nov;6(11):1363-84. doi: 10.1517/17425255.2010.519700. Epub 2010 Sep 27.


Importance of the field: The ATP-binding cassette transporter ABCG2 is a well-known major mediator of multi-drug resistance in cancers. Beyond multi-drug resistance, experimental and recent clinical studies demonstrate a role for ABCG2 as a determinant of drug pharmacokinetic, safety and efficacy profiles.

Areas covered in this review: The clinical evidence of the role of ABCG2 in pharmacokinetics and pharmacodynamics is reviewed. Key questions that arise from the perspective of preclinical drug evaluation are addressed, including the structure of ABCG2 and mechanisms of drug-transporter interactions, mechanisms responsible for the polyspecificity of ABCG2, methods suitable for studying drug-ABCG2 interactions in vitro and in silico prediction of ABCG2 substrates and inhibitors.

What the reader will gain: An update on current knowledge of the importance of ABCG2 in drug disposition with special emphasis on drug development.

Take home message: The field of drug-ABCG2 interaction is rapidly advancing and beginning to expand into clinical practice. However, the structural understanding of drug binding and transport by ABCG2 is still incomplete. Incorporation of novel concepts of drug-transporter interactions such as electrostatic funneling might help explain the multispecificity of ABCG2 and enable in silico predictions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Biological Transport
  • Breast Neoplasms / drug therapy*
  • Clinical Trials as Topic
  • Drug Design
  • Drug Evaluation, Preclinical
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Neoplasm Proteins / metabolism*


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins