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Updated: Jun 23, 2026
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Kevin M Huang1, Alix F Leblanc1, Muhammad Erfan Uddin1
1Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Abstract:
Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin.
Insights
Oxaliplatin chemotherapy causes peripheral neurotoxicity in many cancer patients. Targeting the organic cation transporter 2 (OCT2) in satellite glial cells can prevent this debilitating side effect.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Peripheral neurotoxicity affects up to 90% of colorectal cancer patients on oxaliplatin therapy.
- The role of solute carriers in oxaliplatin-induced neurotoxicity is debated.
- Organic cation transporter 2 (OCT2) is a candidate transporter implicated in drug toxicity.
Purpose of the Study:
- To investigate the role of OCT2 in oxaliplatin-induced peripheral neurotoxicity.
- To evaluate therapeutic strategies targeting OCT2 for neuroprotection.
Main Methods:
- Utilized genetically engineered mouse models to study OCT2 function.
- Employed genetic and pharmacological methods to target OCT2.
- Validated findings in transporter-deficient rats and preclinical colorectal cancer models.
Main Results:
- Demonstrated a critical role for OCT2 in satellite glial cells in oxaliplatin neurotoxicity.
- Showed that targeting OCT2 effectively ameliorates both acute and chronic neurotoxicity.
- Confirmed the relevance of OCT2 in a secondary model organism and preclinical cancer settings.
Conclusions:
- OCT2 in satellite glial cells is a key contributor to oxaliplatin neurotoxicity.
- Targeting OCT2 offers a promising strategy for neuroprotection in cancer patients.
- Pharmacological inhibition of OCT2 could prevent oxaliplatin-induced peripheral neurotoxicity.
