Search for specific inhibitors of multidrug resistance in cancer

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

This paper deals with the theoretical background, methods and clinical significance of the search for specific inhibitors of multidrug resistance (MDR) in cancer. After discussing the basic features of the drug pump membrane proteins (MDR1 and MRP) responsible for this phenomenon, the possible mechanism of action of MDR inhibitors is reviewed. Modulators of drug pump expression may include inhibitors of the transcription and translation, as well as the processing and post-translational modifications of MDR1 and MRP. The function of the drug pumps can be effectively inhibited by substrate analogs, inhibitors of ATP-binding and utilization, specific monoclonal antibodies, and by various agents with still non-specified mechanisms. Basic methods are presented for the in vitro screening of MDR inhibitors in whole cells and in pump protein preparations, as well as for the in vivo assessment of the efficiency and safety of such inhibitors. The review also discusses some current problems and perspectives of MDR modulation in clinical tumor therapy.

Original languageEnglish
Pages (from-to)171-182
Number of pages12
JournalSeminars in Cancer Biology
Volume8
Issue number3
DOIs
Publication statusPublished - Jun 1997

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Multiple Drug Resistance
Neoplasms
Pharmaceutical Preparations
Post Translational Protein Processing
Membrane Proteins
Adenosine Triphosphate
Monoclonal Antibodies
Safety
Proteins
Therapeutics

Keywords

  • Inhibitors
  • MDR1
  • MRP
  • Multidrug transporters
  • P-glycoprotein

ASJC Scopus subject areas

  • Cancer Research

Cite this

Search for specific inhibitors of multidrug resistance in cancer. / Sarkadi, B.; Müller, M.

In: Seminars in Cancer Biology, Vol. 8, No. 3, 06.1997, p. 171-182.

Research output: Contribution to journalArticle

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