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

Szabolcs Modok, Howard R. Mellor, Richard Callaghan

Research output: Contribution to journalReview article

190 Citations (Scopus)


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
Issue number4
Publication statusPublished - Aug 1 2006


ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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