Matches in SemOpenAlex for { <https://semopenalex.org/work/W4381684356> ?p ?o ?g. }
- W4381684356 abstract "Vincristine is a widely used chemotherapeutic drug for the treatment of multiple malignant diseases that causes a dose-limiting peripheral neurotoxicity. There is no clinically effective preventative treatment for vincristine-induced sensory peripheral neurotoxicity (VIPN), and mechanistic details of this side effect remain poorly understood. We hypothesized that VIPN is dependent on transporter-mediated vincristine accumulation in dorsal root ganglion neurons. Using a xenobiotic transporter screen, we identified OATP1B3 as a neuronal transporter regulating the uptake of vincristine. In addition, genetic or pharmacological inhibition of the murine orthologue transporter OATP1B2 protected mice from various hallmarks of VIPN, including mechanical-induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes and neuronal morphology, without negatively affecting plasma levels or antitumor effects of vincristine. Finally, we identified α-tocopherol from an untargeted metabolomics analysis as a circulating endogenous biomarker of neuronal OATP1B2 function, which could serve as a future companion diagnostic to guide dose selection of OATP1B-type transport modulators given in combination with vincristine to prevent VIPN. Collectively, our findings shed light on the fundamental basis of VIPN and provide a rationale for the clinical development of transporter inhibitors to prevent this debilitating side effect." @default.
- W4381684356 created "2023-06-23" @default.
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- W4381684356 date "2023-07-24" @default.
- W4381684356 modified "2023-09-26" @default.
- W4381684356 title "Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy" @default.
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