Breast cancer resistance protein and P-glycoprotein in brain cancer: Two gatekeepers team up

Sagar Agarwal, Anika M.S. Hartz, William F. Elmquist, Björn Bauer

Research output: Contribution to journalReview articlepeer-review

213 Scopus citations


Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies - targeting transporter regulation and direct transporter inhibition - have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a "cooperative team of gatekeepers" at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field.

Original languageEnglish
Pages (from-to)2793-2802
Number of pages10
JournalCurrent Pharmaceutical Design
Issue number26
StatePublished - Sep 2011


  • BCRP
  • Blood-brain barrier
  • Brain cancer
  • Glioblastoma
  • Inhibition
  • Multidrug resistance
  • P-gp
  • Regulation

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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