Mechanisms of multidrug resistance in cancer

Methods Mol Biol. 2010;596:47-76. doi: 10.1007/978-1-60761-416-6_4.

Abstract

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA Damage
  • DNA Repair
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Lipid Bilayers / metabolism
  • Lipid Metabolism
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Neoplastic Stem Cells / metabolism
  • Signal Transduction / physiology
  • Translational Medical Research

Substances

  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Lipid Bilayers
  • Multidrug Resistance-Associated Proteins
  • Cytochrome P-450 Enzyme System