Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance

Donna M. Bradshaw, Robert J. Arceci

Research output: Contribution to journalArticle

Abstract

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.

Original languageEnglish (US)
Pages (from-to)3674-3690
Number of pages17
JournalJournal of Clinical Oncology
Volume16
Issue number11
StatePublished - Nov 1998
Externally publishedYes

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Multiple Drug Resistance
Drug Resistance
Cytotoxins
Pharmaceutical Preparations
Neoplasms
Cell Death
Multidrug Resistance-Associated Proteins
Phenotype
Immunomodulation
P-Glycoprotein
DNA Damage
Therapeutics
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. / Bradshaw, Donna M.; Arceci, Robert J.

In: Journal of Clinical Oncology, Vol. 16, No. 11, 11.1998, p. 3674-3690.

Research output: Contribution to journalArticle

Bradshaw, Donna M. ; Arceci, Robert J. / Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 11. pp. 3674-3690.
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