Multidrug resistance/P-glycoprotein and breast cancer: Review and meta-analysis

Robert Clarke, Fabio Leonessa, Bruce Trock

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Previously untreated breast cancer is relatively sensitive to a range of anticancer drugs. However, exposure to these drugs is often followed by acquisition of multidrug resistance, which is associated with a significantly worse outcome. One of the more widely studied mechanisms of drug resistance is the function of P-glycoprotein (P-gp), a membrane transporter with a wide range of substrates, including several anticancer agents, and a member of the ATP-binding cassette superfamily of proteins. A review of the published literature indicates that P-gp expression is detected in a significant percentage of breast cancers. Moreover, P-gp expression is increased after exposure to chemotherapeutic drugs (particularly those known to be P-gp substrates), and correlates with a worse response to treatment, especially when detected following treatment, in both the adjuvant and neoadjuvant settings. Consequently, P-gp represents a potential biomarker of drug resistance. However, a direct role of P-gp as a cause of clinical drug resistance has not been adequately tested in breast cancer. Future studies aimed at validating the mechanistic role of P-gp should include trials of multidrug resistance reversal using P-gp-specific inhibitors and relating results to the levels of P-gp expression. Future studies should also take into account the potentially multifactorial nature of multidrug resistance.

Original languageEnglish (US)
Pages (from-to)S9-S15
JournalSeminars in oncology
Issue numberSUPPL. 7
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Hematology
  • Oncology


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