Multidrug resistance through the spectacle of P-glycoprotein.
P-glycoprotein (Pgp), coded for by the mdr1 gene, is one of the ABC transporters held responsible for the phenomenon of multidrug resistance (mdr), which is reflected by a rapidly escalating failure of chemotherapy with different classes of cytotoxic agents: anthracyclins, vinca alkaloids, taxanes, epipodophylotoxins. Although overcoming resistance conveyed by Pgp alone may not be sufficient for reaching effective treatment, the abundance of observations available for this paradigmatic multidrug transporter at both in vitro and in vivo setting is a tempting ground for an updated assessment of the main currents of mdr research. In this review we attempt to help keep track of the features of Pgp-mediated drug transport that serve as the major starting points for ongoing efforts of mdr reversal. We will analyze the slowly narrowing gaps that prevail between our ever increasing understanding at the protein, cell and organism level, focusing on the molecular interactions involving Pgp.
Department of Biophysics and Cell Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Katalin
K
Goda
Zsolt
Z
Bacsó
Gábor
G
Szabó
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D000465:Algorithms; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001692:Biological Transport; D003001:Cloning, Molecular; D003630:Daunorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019450:Genes, MDR; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics; D020112:Rhodamine 123 / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020112:Rhodamine 123; D003630:Daunorubicin