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Mechanisms and strategies to overcome multiple drug resistance in cancer
Authors:Ozben Tomris
Institution:Akdeniz University, Faculty of Medicine, Department of Biochemistry, 07070 Antalya, Turkey. ozben@akdeniz.edu.tr
Abstract:One of the major problems in chemotherapy is multidrug resistance (MDR) against anticancer drugs. ATP-binding cassette (ABC) transporters are a family of proteins that mediate MDR via ATP-dependent drug efflux pumps. Many MDR inhibitors have been identified, but none of them have been proven clinically useful without side effects. Efforts continue to discover not toxic MDR inhibitors which lack pharmacokinetic interactions with anticancer drugs. Novel approaches have also been designed to inhibit or circumvent MDR. In this review, the structure and function of ABC transporters and development of MDR inhibitors are described briefly including various approaches to suppress MDR mechanisms.
Keywords:MDR  multidrug resistance  MRP  multidrug resistance protein  ATP  adenosinetriphosphate  ABC  ATP-binding cassette  TMD  transmembrane domains  P-gp  P-glycoprotein  MRP1  MDR related protein  BCRP  breast cancer resistance protein  ABC-P  ABC transporter in placenta  LRP  lung resistance-related protein  MVP  major vault protein  CMOAT  canalicular multi-organic anion transporter  CYP3A4  Cytochrome p450 3A4  SXR  steroid and xenobiotic receptor  GC  glucosylceramide  GCS  glucosylceramide synthase  GSH  glutathione  NAC  N-acetylcysteine  BSO  dl-buthionine (S" target="_blank">dl-buthionine (S  R)-sulfoximine  HEK  human embryonic kidney  ROS  reactive oxygen species
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