Development of multidrug-resistance convertors: sense or nonsense?
This review describes the clinical relevance of the two drug transporters P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) and the in vitro phenomenon which is referred to as multidrug resistance (MDR). The attempts to try to block these resistance mechanisms are summarized with specific attention for the intentionally designed "second generation" MDR-convertors. Potential explanations of the limited clinical success rate are given and recommendations for the design of future studies provided.
van Zuylen
L
L
Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, The Netherlands. zuylen@onch.azr.nl
Nooter
K
K
Sparreboom
A
A
Verweij
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000502:physiology*; D000166:Acridines / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins; D003524:Cyclosporins / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000032:analysis / Q000502:physiology*; D044005:Tetrahydroisoquinolines
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D001426:Bacterial Proteins; D003524:Cyclosporins; D007546:Isoquinolines; D010880:Piperidines; D011725:Pyridines; D044005:Tetrahydroisoquinolines; C106077:biricodar; C108269:BSase protein, Bacillus subtilis; D012697:Serine Endopeptidases; C083501:Elacridar; C070272:valspodar