title: The importance of breast cancer resistance protein to the kidneys excretory function and chemotherapeutic resistance.
abstract: The relevance of membrane transporters gained momentum in recent years and it is now widely recognized that transporters are key players in drug disposition and chemoresistance. As such, the kidneys harbor a variety of drug transporters and are one of the main routes for xenobiotic excretion. The breast cancer resistance protein (BCRP/ABCG2) is widely accepted as a key mediator of anticancer drug resistance and is a prominent renal drug transporter. Here, we review the role of BCRP in both processes and present a multitude of variables that can influence its activity. An increasing number of renally cleared chemotherapeutics, including tyrosine kinase inhibitors, described as BCRP substrates can modulate its activity via transcription factors and cellular signaling pathways, such as the phosphoinositide 3-kinase (PI3K) pathway. In addition to pharmacological actions, genetic variations, as well as differences between species and gender can affect BCRP function, which are also discussed. Furthermore, the role of BCRP in light of cancer treatments and the implications for novel therapeutic interventions that take into account renal function are discussed.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands.
authors.forename: Pedro
authors.initials: P
authors.lastname: Caetano-Pinto
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands.
authors.forename: Jitske
authors.initials: J
authors.lastname: Jansen
authors.affiliation: The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yehuda G
authors.initials: YG
authors.lastname: Assaraf
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands. Electronic address: r.masereeuw@uu.nl.
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Masereeuw
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D065667:Renal Elimination / Q000502:physiology*; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D058539:Phosphatidylinositol 3-Kinase; D011505:Protein-Tyrosine Kinases
keywords: BCRP; Chemoresistance; Drug transport; Renal excretion