Multidrug efflux pumps and cancer stem cells: insights into multidrug resistance and therapeutic development

Clin Pharmacol Ther. 2011 Apr;89(4):491-502. doi: 10.1038/clpt.2011.14. Epub 2011 Mar 2.

Abstract

Stem cells possess the dual properties of self-renewal and pluripotency. Self-renewal affords these populations the luxury of self-propagation, whereas pluripotency allows them to produce the multitude of cell types found in the body. Protection of the stem cell population from damage or death is critical because these cells need to remain intact throughout the life of an organism. The principal mechanism of protection is through expression of multifunctional efflux transporters--the adenosine triphosphate-binding cassette (ABC) transporters that are the "guardians" of the stem cell population. Ironically, it has been shown that these ABC efflux pumps also afford protection to cancer stem cells (CSCs), shielding them from the adverse effects of chemotherapeutic insult. It is therefore imperative to gain a better understanding of the mechanisms involved in the resistance of stem cells to chemotherapy, which could lead to the discovery of new therapeutic targets and improvement of current anticancer strategies.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Delivery Systems
  • Drug Design
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplastic Stem Cells / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents