Diagnostics of multidrug resistance in cancer.
Multidrug resistance (MDR), caused by the overexpression of two membrane proteins, MDR1-Pgp and/or MRP, is a major obstacle in the chemotherapy of cancer. The proper laboratory diagnosis of clinical multidrug resistance is still an unresolved question, and this uncertainty, in a vicious cycle, does not allow the correct evaluation of the clinical relevance of the MDR phenomenon. More-over, inefficient MDR diagnostics hinders the development of effective resistance-modulation strategies. In this review, after describing the basic features of the MDR drug pump proteins, the currently employed diagnostic methods are discussed. We suggest that a quantitative, functional method developed in our laboratory may provide a major help in the laboratory assessment of cancer MDR.
Szakács
G
G
Membrane Research Group of the Hungarian Academy of Sciences, National Institute of Haematology and Immunology, Budapest, Hungary.
Jakab
K
K
Antal
F
F
Sarkadi
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D003933:Diagnosis; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011454:Prostaglandins A / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D005452:Fluoresceins; D005456:Fluorescent Dyes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011454:Prostaglandins A; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014700:Verapamil; C085925:calcein AM; C100573:prostaglandin A1