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Review
. 2011 Apr;12(4):595-608.
doi: 10.2174/138920111795163913.

The challenge of exploiting ABCG2 in the clinic

Robert W Robey  1 , Caterina Ierano, Zhirong Zhan, Susan E Bates
Affiliations
Review

The challenge of exploiting ABCG2 in the clinic

Robert W Robey et al. Curr Pharm Biotechnol. 2011 Apr.

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.

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Figures

Figure 1
Figure 1
Schematic representation of ABCG2 expression in normal tissues. Arrows indicate direction of substrate transport. In the brain and testis, ABCG2 is expressed mainly in the blood vessel endothelium, forming part of the blood-brain and blood-testis barrier, respectively.
See this image and copyright information in PMC

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