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lüll The emerging pharmacotherapeutic significance of the breast cancer resistance protein (ABCG2) Hardwick LJ; Velamakanni S; van Veen HWBr J Pharmacol 2007[May]; 151 (2): 163-74The breast cancer resistance protein (also termed ABCG2) is an ATP-binding cassette transporter, which mediates the extrusion of toxic compounds from the cell, and which was originally identified in relation to the development of multidrug resistance of cancer cells. ABCG2 interacts with a range of substrates including clinical drugs but also substances such as sterols, porphyrins and a variety of dietary compounds. Physiological functions of ABCG2 at both cellular and systemic levels are reviewed. For example, ABCG2 expression in erythrocytes may function in porphyrin homeostasis. In addition, ABCG2 expression at apical membranes of cells such as hepatocytes, enterocytes, endothelial and syncytiotrophoblast cells may correlate to protective barrier or secretory functions against environmental or clinically administered substances. ABCG2 also appears influential in the inter-patient variation and generally poor oral bioavailability of certain chemotherapeutic drugs such as topotecan. As this often precludes an oral drug administration strategy, genotypic and environmental factors altering ABCG2 expression and activity are considered. Finally, clinical modulation of ABCG2 activity is discussed. Some of the more recent strategies include co-administered modulating agents, hammerhead ribozymes or antisense oligonucleotides, and with specificity in cell targeting, these may be used to reduce drug resistance and increase drug bioavailability to improve the profile of chemotherapeutic efficacy versus toxicity. While many such strategies remain in relative infancy at present, increased knowledge of modulators of ABCG2 could hold the key to novel approaches in medical treatment.|ATP Binding Cassette Transporter, Subfamily G, Member 2[MESH]|ATP-Binding Cassette Transporters/antagonists & inhibitors/metabolism/*physiology[MESH]|Acridines/therapeutic use[MESH]|Antineoplastic Agents/therapeutic use[MESH]|Drug Resistance, Multiple/*physiology[MESH]|Drug Resistance, Neoplasm[MESH]|Humans[MESH]|Neoplasm Proteins/antagonists & inhibitors/metabolism/*physiology[MESH]|Neoplasms/drug therapy/metabolism/pathology[MESH]|Technology, Pharmaceutical/methods/trends[MESH]|Tetrahydroisoquinolines/therapeutic use[MESH]|Topotecan/therapeutic use[MESH] |