Non-P-glycoprotein drug export mechanisms of multidrug resistance

Semin Hematol. 1997 Oct;34(4 Suppl 5):20-4.

Abstract

A variety of cellular mechanisms of multidrug resistance (MDR) have been identified in human drug-resistant cell lines, and may play an important role in the clinical response of hematologic malignancies to chemotherapy. P-glycoprotein (P-gp)-mediated drug efflux is the most well-characterized cellular mechanism of MDR; however, several other non-P-gp membrane transporter proteins have also been implicated in the development of an MDR phenotype in hematologic malignancies. These include the MDR-related protein (MRP), the lung-resistance protein (LRP), and the transporter of antigenic peptides (TAP). The transporter proteins MRP and TAP are both members of the adenosine triphosphate (ATP)-binding cassette (ABC) family of transmembrane transporters, but each has distinct differences in substrate specificity. Despite effective modulation of P-gp, one or more of these alternate mechanisms of drug resistance may contribute to an MDR phenotype in tumor cell lines. Development of multifunctional MDR modulators or novel therapeutics may be necessary to effectively circumvent MDR in hematologic malignancies.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Drug Resistance, Multiple* / genetics
  • Drug Resistance, Neoplasm* / genetics
  • Drug Synergism
  • Humans
  • Neoplasm Proteins / genetics
  • Vault Ribonucleoprotein Particles*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein