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

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