Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2

Pharmacogenomics. 2005 Mar;6(2):115-38. doi: 10.1517/14622416.6.2.115.

Abstract

ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein) and ABCG2 (breast cancer-resistance protein [BCRP], mitoxantrone-resistance protein [MXR], or ABC transporter in placenta [ABCP]), are also known to influence oral absorption and disposition of a wide variety of drugs. As a result, the expression levels of these proteins in humans have important consequences for an individual's susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. Naturally occurring variants in ABC transporter genes have been identified that might affect the function and expression of the protein. This review focuses on recent advances in the pharmacogenetics of the ABC transporters ABCB1 and ABCG2, and discusses potential implications of genetic variants for the chemotherapeutic treatment of cancer.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / physiology
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Area Under Curve
  • Biological Transport / physiology
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / physiology
  • Polymorphism, Genetic

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Organic Anion Transporters