Transporters in drug resistance

De Rossi E, Ainsa JA, Riccardi G. Role of mycobacterial efflux transporters in drug resistance an unresolved question. FEMS Microbiol Rev. 2006 30 36-52. 

Glavinas, H. Krajcsi, P. Cserepes, J. Sarkadi, B. The role of ABC transporters in drug resistance, metabolism, and toxicity. Curr. Drug Deliv. 2004, 1, 27 2. 

Sipos, G. and Kuchler, K. (2006) Fungal ATP-binding cassette (ABC) transporters in drug resistance detoxification. Current Drug Targets, 7, 471-4S1. 

TFP (5) was the first phenothiazine demonstrated to modulate MDR in drug-resistant P338 murine leukemia cells. TFP (5) enhanced intracellular accumulation of vincristine and adriamycin (77) in resistant tumor cells by inhibiting outward transport of these anticancer drugs [167]. Studies per-... 

The MDR transporter is of importance in drug resistance in antiprotozoal and anticancer chemotherapy and hence compounds that inhibit this transporter are potentially very useful as adjuncts to chemotherapy to overcome such drug resistance (Table 13.7). This chapter also deals with numerous plant-derived compounds that inhibit various other enzymes (Table 13.8). 

The proteins whose abundances are altered in the plasma membrane in drug-resistant cells (Table 13.2) include those involved in increased amino acid uptake (4F2 cell-surface antigen heavy chain, large neutral amino acids transporter small subunit-1), reduced glucose uptake (stomatin, facilitated glucose transport... 

Many tissues also express the same drug export pumps that occur in the barrier epithelial tissues (e.g./ MDR/ MRP/ MXR)/ and these may be important in normal tissues/ as well as in drug-resistant cancers. For example/ P-gp may contribute to resistance to pep-tidomimetic HIV protease inhibitors (e.g./ indinavir/ saquinavir/ and nelfinavir) in AIDS patients. These drugs are substrates for P-gp/ and this transporter... 

The responses of these three cancer types were found to differ during clinical trials of MDR-1 inhibitors (123). For the first class, MDR-1 inhibition has had little effect on the efficacy of the cancer therapy. It appears that too many other transporters and drug resistance mechanisms are present in front-line defense organs such as kidney, liver, and intestine. For the second class, at least transiently improved responses to anticancer drugs have been seen with MDR-1 inhibitor cotherapy. However, a second relapse is seen as other transport... 

Breast Cancer Resistance Protein (BCRP) BCRP is one of the newer ABC transport proteins to be examined. The transporter was first identified in drug-resistant breast cancer cells.165 Structurally, BCRP differs from both P-gp and MRP in that it is a half-transporter and requires the formation of a protein dimer for functional transporter activity.166 There is a great deal of substrate overlap between P-gp and BCRP.167 In addition to being overexpressed in various tumor cells, BCRP has been detected in normal tissues such as the placenta, small intestine, liver, and capillary and venous endothelial cells.156... 

Ruth. A.. Stein. W.D., Rose, E.. and Roninson, LB. (2001) Coordinate changes in drug resistance and drug-induced conformational transitions in altered-function mutants of the multidrug transporter P-glycoprotein. Biochemistry, 40 (14), 4332-4339. 

Lang, T.T., Seiner, M., Young, J.D., and Cass, C.E. (2001) Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Molecular Pharmacology, 60 (5), 1143-1152. 

Tew, K, D., Bomber, A. M., and Hoffman, S. J., Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines. Cancer Res. 48, 3622-3625 (1988). Tipping, E., and Ketterer, B., The influence of soluble binding proteins on lipophile transport and metabolism in hepatocytes. Biochem. J. 195, 441 52 (1981). 

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