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Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11199-204. doi: 10.1073/pnas.1305321110. Epub 2013 Jun 17.

Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2.

Author information

1
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

Oxaliplatin is an integral component of colorectal cancer therapy, but its clinical use is associated with a dose-limiting peripheral neurotoxicity. We found that the organic cation transporter 2 (OCT2) is expressed on dorsal root ganglia cells within the nervous system where oxaliplatin is known to accumulate. Cellular uptake of oxaliplatin was increased by 16- to 35-fold in cells overexpressing mouse Oct2 or human OCT2, and this process was associated with increased DNA platination and oxaliplatin-induced cytotoxicity. Furthermore, genetic or pharmacologic knockout of Oct2 protected mice from hypersensitivity to cold or mechanical-induced allodynia, which are established tests to assess acute oxaliplatin-induced neurotoxicity. These findings provide a rationale for the development of targeted approaches to mitigate this debilitating toxicity.

KEYWORDS:

chemotherapy; neuropathy; solute carriers

PMID:
23776246
PMCID:
PMC3704038
DOI:
10.1073/pnas.1305321110
[Indexed for MEDLINE]
Free PMC Article

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