BCRP

Breast Cancer Resistance Protein (BCRP, also known as MXR or ABCP), first cloned from mitoxantrone and anthracycline-resistant breast and colon cancer cells [188, 189] is a half-transporter efflux pump believed to function as a homo-or hetero-dimer. Following its identification, BCRP-mediated drug resistance was observed for topoisomerase inhibitors including camptothecins [190, 191] and in-dolocarbazoles [192]. In normal tissues, BCRP was detected in placental syncytio-trophoblasts, hepatocyte canalicular membrane, apical intestinal epithelia and vascular endothelial cells [193]. These findings support the important role BCRP plays in modulating topotecan bioavailability, fetal exposure and hepatic elimination [194]. Considering that the substrates and tissue distributions for BCRP overlap somewhat with MDR1 and MRPs [195], additional studies will be required to define the relative contribution of each of these transporters in the overall and tis- 

As SNP discovery technologies become mainstream research tools, the importance of genotype-phenotype relationships will continue to be a focus in pharma-cogenomic research. Not only will characterization of drug transporter polymorphisms enhance our insight of the molecular mechanisms involved in transporter function, it is likely that such findings will become important components of individualized drug therapy in the future. 

2 Lander ES, Linton LM, Birren B, Nus-baum C, Zody MC, Baldwin J et al. Initial sequencing and analysis of the human genome. Nature 2001  

3 Tsuji A, Tamai I. Carrier-mediated intestinal transport of drugs. Pharm Res 1996 13(7) 963—977. 

4 Suzuki H, Sugiyama Y. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine. Eur J Pharm Sci 2000 12( 1) 3— 12. 

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Most ABC-transporters, especially those located in the plasma membrane, are phosphorylated and glycosylated transmembrane proteins of different molecular weights (e.g., P-gp 170 kDa MRP2 190 kDa BCRP 72 kDa). Topologically, most ABC-transporter show a similar structure they are organized in two transmembrane domains (TMD), each consisting of six... 

BCRP (ABCG2) Cisplatin, folate, methotrexate, mitoxantrone, topotecan, irinotecan, steroids (cholesterol, testosterone, progesterone), certain chlorophyll metabolites, and others... 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Krishnamurthy P, Schuetz JD (2006) Role of ABCG2/ BCRP in biology and medicine. Annu Rev Pharmacol Toxicol 46 381-410... 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Breast cancer resistance protein (BCRP) is another ATP-dependent efflux transporter that confers resistance to a variety of anticancer agents, including... 

Importantly, the currently available transporter models only cover a small fraction of all transporters involved in drug disposition. Other than incorporating current stand-alone transporter models into systemic models to directly predict drug pharmacokinetic properties, continued efforts are still needed to investigate other transporters such as MRP, BCRP, NTCP, and OAT, to get a more complete understanding of the drug pharmacokinetic profile. 

The study of active transport mechanisms has grown substantially in recent years, with transport proteins such as P-gp, BCRP, and MRP-2 among the most studied [59]. Several types of in vitro assays to assess substrates of transporters have been established these include assays directed toward intestinal and biliary efflux [60]. Assays that measure passive and active transport are also used to assess penetration of the blood-brain barrier. In addition to the assays described above, transfected cell lines that overexpress transporters present in the blood-brain barrier are also employed [61]. 

Biliary Excretion Mediated by Breast Cancer-Resistant Protein (BCRP)... 

Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC et al. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res 1999 ... 

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