Clinical management of recurrent breast cancer: development of multidrug resistance (MDR) and strategies to circumvent it

Semin Oncol. 2005 Dec;32(6 Suppl 7):S16-21. doi: 10.1053/j.seminoncol.2005.09.011.

Abstract

The multidrug resistance (MDR) phenotype is often associated with recurrent breast cancer. Many cytotoxic agents used to treat breast cancer, such as anthracyclines and taxanes, are susceptible to MDR-mediated loss of sensitivity to these agents. Overexpression of mdr-1/P-glycoprotein (P-gp) is one of the main mechanisms underlying the development of the MDR phenotype. Also involved in the development of the MDR phenotype are other proteins from the ATP-binding cassette family of transporters (eg, MRP, BCRP), as well as alterations of tumor targets and their downstream effector molecules. Additionally, P-gp expression in other anatomic locations (such as the brush border of the gastrointestinal epithelium and blood-brain barrier) may further compromise the success of treatment for patients with breast cancer. Several strategies have been developed to overcome or circumvent MDR, mostly through inhibition or modulation of P-gp. Despite successful proof of concept in the laboratory, to date none of these agents has had a major impact in the clinic.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • Antineoplastic Agents / therapeutic use*
  • Basigin / physiology
  • Breast Neoplasms / therapy*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Recurrence, Local / drug therapy*

Substances

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