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Drug Transporters in Chemotherapy Induced Peripheral Neurotoxicity:Current Knowledge and Clinical Implications

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Several antineoplastic drugs induce severe and dose-limiting peripheral neurotoxicity that can significatly affect the quality of life of cancer patients and cause chronic discomfort. Despite extensive investigation, the fine mechanisms of this side-effect remain unclear.

It has recently been suggested that several classes of drug transporters are involved in the genesis of chemotherapyinduced peripheral neurotoxicity. Furthermore, the differential distribution and activity of these transporters could also explain the higher sensitivity of the peripheral rather than central nervous system tissues to the toxic action of the anticancer agents. These observations may have important therapeutic implications. In fact, the characterization of the proteins that mediate significant transport of clinically relevant drugs in the nervous system, and the understanding of their changes in the different pathological conditions are important in order to elucidate pathogenetic mechanisms and to identify new potential therapeutic targets so as to limit the severity of chemotherapy-induced peripheral neurotoxicity.

This review will be focused on the most recent research progress on the role of drug transporters in chemotherapy-induced peripheral neurotoxicity, and we will discuss the possibility of targeting these transporters as a new and interesting potential strategy for the treatment of the neurotoxic side-effects of antineoplastic drugs.

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Keywords: ATP BINDING CASSETTE; DRG neuronal expression; P-Glycoprotein; Platinum drugs; Saccharomyces cerevisiae; Transporter; anthracyclines; antineoplastic drugs; antinociceptive; aorta; astrocyte; astrocytes; brain; brain parenchyma; capillary endothelium cells; central nervous system; cerebellum; chemotherapy; chemotherapy-induced neurotoxicity; cytochrome; dopamine; dorsal root ganglia; dorsal root ganglia (DRG); dose; doxorubicin; epilepsy; etoposide; excretory organs; fluorescence; glucuronic acid; hippocampus; hybridization; immunohistochemistry; methionine; multidrug resistance gene; neurotoxic; neurotoxic drugs; nucleus accumbens; ovarian cancer; oxaliplatin; oxidative stress; paclitaxel; peripheral neuropathy; pharmacodynamics; pharmacokinetics; platinum drug; prostate; pyramidal cells; rate-limiting steps; skeletal muscle; spinal cord; striatum; tail-flick pain tests; two-dimensional structure; uptake; vinblastine; vinca alkaloids

Document Type: Research Article

Publication date: 2011-01-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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