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

C.      Ceresa; G.      Cavaletti

doi:10.2174/092986711794839160

Abstract

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.

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