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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
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Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Published on: April 26, 2012

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OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity

Alix F Leblanc1, Jason A Sprowl2, Paola Alberti3

  • 1Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.

The Journal of Clinical Investigation
|January 17, 2018
PubMed

Insights

Researchers identified the organic anion-transporting polypeptide B2 (OATP1B2) as a key factor in paclitaxel-induced neurotoxicity. Blocking OATP1B2 protected mice from nerve damage, offering a potential therapeutic strategy for managing this common chemotherapy side effect.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Oncology

Background:

  • Paclitaxel is a vital chemotherapy agent.
  • Paclitaxel causes dose-limiting peripheral neurotoxicity.
  • The mechanisms initiating paclitaxel neurotoxicity are currently unknown.

Purpose of the Study:

  • To identify the molecular mediators of paclitaxel-induced neurotoxicity.
  • To investigate the role of solute carrier organic anion-transporting polypeptide B2 (OATP1B2) in paclitaxel neurotoxicity.
  • To explore potential therapeutic strategies for mitigating paclitaxel neurotoxicity.

Main Methods:

  • Genetic and pharmacologic knockout of OATP1B2 in mice.
  • Assessment of mechanical allodynia and thermal hyperalgesia.
  • Measurement of digital maximal action potential amplitudes.
  • Inhibition of OATP1B2 function using nilotinib.

Main Results:

  • OATP1B2 was identified as a mediator of paclitaxel-induced neurotoxicity.
  • OATP1B2 knockout protected mice from paclitaxel-induced allodynia and hyperalgesia.
  • OATP1B2 knockout prevented changes in digital maximal action potential amplitudes.
  • Nilotinib noncompetitively inhibited OATP1B2 function without affecting paclitaxel's anticancer properties.

Conclusions:

  • OATP1B2 plays a critical role in the pathogenesis of paclitaxel neurotoxicity.
  • Targeting OATP1B2 offers a potential strategy to manage paclitaxel-induced peripheral neurotoxicity.
  • Nilotinib represents a potential therapeutic agent for preventing paclitaxel neurotoxicity.
Keywords:
CancerOncologyToxins/drugs/xenobioticsTransport

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