Reversing agents for ATP-binding cassette (ABC) transporters: application in modulating multidrug resistance (MDR)

Curr Med Chem Anticancer Agents. 2004 Jan;4(1):43-52. doi: 10.2174/1568011043482197.

Abstract

One of the main reasons for the failure in cancer chemotherapy is the existence of multidrug resistance (MDR) mechanisms. One form of MDR phenotype is contributed by a group of plasma membrane proteins that belong to a large superfamily of proteins called the ATP-binding cassette (ABC) transporters. There has been intense search for compounds, which can act at reversing MDR phenotype exhibited by ABC transporters such as P-glycoprotein (P-gp), multidrug-resistance protein (MRP) and breast cancer resistance protein (BCRP). Reversing agents can be designed to target MDR-associated ABC transporters at three levels - the protein, mRNA or DNA level. This review aims at describing, over-viewing and discussing currently known MDR reversing agents, which have been shown to act at either of the three levels against ABC transporters. Other potential agents and strategies, which can be used to reverse the MDR phenotype, are also discussed.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Phenotype

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents