Mechanisms and strategies to overcome multiple drug resistance in cancer

FEBS Letters - Tập 580 - Trang 2903-2909 - 2006
Tomris Ozben1
1Akdeniz University, Faculty of Medicine, Department of Biochemistry, 07070 Antalya, Turkey

Tóm tắt

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.


Tài liệu tham khảo

10.1111/j.1365-2362.2004.01411.x 10.1186/1475-2867-5-22 Liscovitch M., 2002, Cancer multidrug resistance: a review of recent drug discovery research, IDrugs., 5, 349 10.1177/107327480301000207 10.1186/1475-2867-5-30 10.1146/annurev.pharmtox.39.1.361 10.1016/S0928-0987(00)00114-7 Stavrovskaya A.A., 2000, Cellular mechanisms of multidrug resistance of tumor cells, Biochemistry (Mosc)., 65, 95 10.1038/nrc706 10.1634/theoncologist.8-5-411 10.1101/gr.GR-1649R 10.2174/1566524013364194 10.1016/j.febslet.2004.03.123 10.1038/346362a0 10.1074/jbc.271.40.24617 10.1074/jbc.M211758200 Abolhoda A., 1999, Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin, Clin. Cancer Res., 5, 3352 10.1126/science.1360704 10.1073/pnas.95.26.15665 10.1016/0959-8049(96)00091-3 Ford J.M., 1990, Pharmacology of drugs that alter multidrug resistance in cancer, Pharmacol. Rev., 42, 155 10.1002/(SICI)1096-911X(200004)34:4<242::AID-MPO2>3.0.CO;2-U Fischer V., 1998, The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A Implications for drug–drug interactions and pharmacological activity of the main metabolite, Drug Metab. Dispos., 26, 802 10.1023/A:1006487003814 10.1016/S0960-894X(99)00030-X Newman M.J., 2000, Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance, Cancer Res., 60, 2964 Dantzig A.H., 1999, Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities, J. Pharmacol. Exp. Ther., 290, 854 10.1016/S0065-2571(96)00021-0 10.1016/0959-8049(96)00065-2 10.1074/jbc.275.10.7138 Lucci A., 1999, Ceramide toxicity and metabolism differ in wild-type and multidrug-resistant cancer cells, Int. J. Oncol., 15, 535 10.1074/jbc.271.32.19530 Lucci A., 1998, Glucosylceramide: a marker for multiple-drug resistant cancers, Anticancer Res., 18, 475 10.1074/jbc.274.2.1140 Lucci A., 1999, Modification of ceramide metabolism increases cancer cell sensitivity to cytotoxics, Int. J. Oncol., 15, 541 10.1074/jbc.272.3.1682 10.1002/(SICI)1097-0142(19990715)86:2<300::AID-CNCR14>3.0.CO;2-H 10.1093/jnci/93.5.347 Wilson W.H., 2000, Chemotherapy sensitization by rituximab: experimental and clinical evidence, Semin. Oncol., 27, 30 10.1016/j.febslet.2005.06.051 Kanadaswami C., 2005, The antitumor activities of flavonoids, In Vivo, 19, 895 10.1016/j.jss.2004.11.011 10.18388/abp.2005_3404