Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer

S. Modok, Howard R. Mellor, Richard Callaghan

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Early publications using cultured cancer cells immediately recognized the phenomenon of resistance to anticancer agents. However, it was not until 1973 that it was first demonstrated that a major factor in the resistance of cancer cells was that of reduced drug accumulation. This year marks the 30th anniversary of the discovery by Juliano and Ling that P-glycoprotein mediates this active efflux of chemotherapeutic drugs from cancer cells. Since this seminal finding, the investigation of P-glycoprotein (MDR1, ATP binding cassette [ABC]B1) has proceeded with great vigour. However, it soon became apparent that P-glycoprotein was not expressed in all drug-resistant cells that displayed an accumulation deficiency, which led to the discovery of other ABC transporters involved in drug efflux. In 1992, the multidrug resistance-associated protein (MRP1, ABCC1) was identified in small cell lung cancer followed by breast cancer resistance protein (mitoxantrone resistance protein, ABCG2) in 1999. After three decades of research, can we confidently define the contribution of multidrug resistance transporters to chemoresistance and do we have clinically useful drugs to sensitise cancers?

Original languageEnglish
Pages (from-to)350-354
Number of pages5
JournalCurrent Opinion in Pharmacology
Volume6
Issue number4
DOIs
Publication statusPublished - Aug 2006

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Multiple Drug Resistance
P-Glycoprotein
Pharmaceutical Preparations
Neoplasms
Breast Neoplasms
Multidrug Resistance-Associated Proteins
Mitoxantrone
ATP-Binding Cassette Transporters
R Factors
Small Cell Lung Carcinoma
Anniversaries and Special Events
Antineoplastic Agents
Cultured Cells
Adenosine Triphosphate
Research
Proteins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. / Modok, S.; Mellor, Howard R.; Callaghan, Richard.

In: Current Opinion in Pharmacology, Vol. 6, No. 4, 08.2006, p. 350-354.

Research output: Contribution to journalArticle

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