The role of P-glycoprotein in drug resistance in multiple myeloma

Leuk Lymphoma. 2015 Jan;56(1):26-33. doi: 10.3109/10428194.2014.907890. Epub 2014 Jun 5.

Abstract

Multiple myeloma (MM) is a malignant neoplastic cancer of the plasma cells that involves the bone marrow. The majority of patients with MM initially respond to chemotherapy, but they eventually become resistant to later drug therapy. One of the reasons for drug resistance in patients with MM is efflux transporters. P-glycoprotein (P-gp) is the most studied of the multidrug resistance proteins, and is up-regulated in response to many chemotherapeutic drugs. This up-regulation of P-gp causes a decrease in the intracellular accumulation of these drugs, limiting their therapeutic efficacy. In this review, we focus on the role of P-gp in drugs used for patients with MM. P-gp has been found to be an important factor with regard to drug resistance in many of the drug classes used in the treatment of MM (proteasome inhibitors, anthracyclines, alkylating agents and immunomodulators are examples). Thus, our further understanding of its mechanism and inhibitory effects will help us decrease drug resistance in patients with MM.

Keywords: Drug resistance; chemotherapeutic approaches; myeloma.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism

Substances

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