ArticleJCI insight2023
Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Extrapolating Vincristine-Induced Peripheral Neuropathy From Caucasian to Kenyan Populations: Impact of Type I and Type II Selection Bias.CPT: pharmacometrics & systems pharmacology · 2026Article
- Proximity Labelling Reveals the Compartmental Proteome of Murine Sensory Neurons.European journal of pain (London, England) · 2026Article
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Regulation of hepatic organic anion transporting polypeptide 1B-type transport function by the protein kinase LYN.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Strain-dependent neuronal disposition and toxicity of paclitaxel in mice.ASPET discovery · 2025Article
- Review
- Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen.Cancer research communications · 2024Article
- Vincristine Disposition and Neurotoxicity Are Unchanged in Humanized CYP3A5 Mice.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 4 countries.
Funding
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 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, and it could serve as a 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.