The challenge of exploiting ABCG2 in the clinic

Robert W. Robey, Caterina Ierano, Zhirong Zhan, Susan E. Bates

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

ABCG2, or breast cancer resistance protein (BCRP), is an ATP-binding cassette half-transporter that has been shown to transport a wide range of substrates including chemotherapeutics, antivirals, antibiotics and flavonoids. Given its wide range of substrates, much work has been dedicated to developing ABCG2 as a clinical target. But where can we intervene clinically and how can we avoid the mistakes made in past clinical trials targeting P-glycoprotein? This review will summarize the normal tissue distribution, cancer tissue expression, substrates and inhibitors of ABCG2, and highlight the challenges presented in exploiting ABCG2 in the clinic. We discuss the possibility of inhibiting ABCG2, so as to increase oral bioavailability or increase drug penetration into sanctuary sites, especially the central nervous system; and at the other end of the spectrum, the possibility of improving ABCG2 function, in the case of gout caused by a single nucleotide polymphism. Together, these aspects of ABCG2/BCRP make the protein a target of continuing interest for oncologists, biologists, and pharmacologists.

Original languageEnglish
Pages (from-to)595-608
Number of pages14
JournalCurrent Pharmaceutical Biotechnology
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Breast Neoplasms
Proteins
ATP-Binding Cassette Transporters
Gout
Normal Distribution
P-Glycoprotein
Tissue Distribution
Flavonoids
Biological Availability
Antiviral Agents
Nucleotides
Central Nervous System
Clinical Trials
Anti-Bacterial Agents
Pharmaceutical Preparations
Neoplasms
Oncologists

Keywords

  • ABCG2/BCRP
  • Blood-brain barrier
  • CNS penetration
  • Drug resistance
  • Gout
  • Oral bioavailability
  • Q141K
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Biotechnology

Cite this

The challenge of exploiting ABCG2 in the clinic. / Robey, Robert W.; Ierano, Caterina; Zhan, Zhirong; Bates, Susan E.

In: Current Pharmaceutical Biotechnology, Vol. 12, No. 4, 04.2011, p. 595-608.

Research output: Contribution to journalArticle

Robey, Robert W. ; Ierano, Caterina ; Zhan, Zhirong ; Bates, Susan E. / The challenge of exploiting ABCG2 in the clinic. In: Current Pharmaceutical Biotechnology. 2011 ; Vol. 12, No. 4. pp. 595-608.
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