Neuronal drug transporters in platinum drugs-induced peripheral neurotoxicity

Anticancer Res. 2014 Jan;34(1):483-6.

Abstract

To gain a better insight into the neurotoxicity of platinum drugs, it is important to increase our knowledge over the phenomena allowing their entry into dorsal root ganglia neurons. A deeper understanding of platinum-drug transport mechanisms in neurons would represent not only a step forward in the pathogenetic interpretation of their neurotoxicity, but would also disclose possible treatment options to prevent this severe side-effect achievable through modulation of transporter activity. Copper transporters and organic cation transporters have been identified as putative targets for the pharmacological modulation of neuronal cell accumulation of platinum drugs and damage, and this possibility has been demonstrated by animal studies. The modulation of drug transporter activity is a promising strategy to limit the neurotoxicity of platinum drugs, provided that a) complete characterization of drug transporters is obtained and b) selective neuronal activity is targeted without reducing anticancer drug efficacy.

Keywords: Copper transporters; neuron; organic cationic transporters; platinum drug-induced neurotoxicity; review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / metabolism
  • Organoplatinum Compounds / adverse effects*
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / metabolism

Substances

  • Antineoplastic Agents
  • Membrane Transport Proteins
  • Organoplatinum Compounds