# The role of cell-specific TLR-4 signaling in oxaliplatin-induced peripheral neuropathy

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $432,476

## Abstract

Oxaliplatin-associated Chemotherapy-induced Peripheral Neuropathy (CIPN) is a frequent, potentially
severe and dose-limiting toxicity of colorectal cancer treatment. The overall incidence of CIPN is estimated to be
approximately upwards of 40% in patients. CIPN can persist for months to years beyond chemotherapy
completion, causing significant challenges for cancer survivors due to its negative influence on quality of life
(QOL). CIPN represents an important challenge because of the lack of treatment that can effectively prevent or
mitigate this adverse drug effect. We have identified specific receptor-mediated pathways which contribute to
increases in ion current as a potential therapeutic target for the treatment or prevention of CIPN. Noteworthy,
several ion channel modulators central to CIPN treatment are FDA-approved drugs used for other disease
conditions. This proposal highlights a multidisciplinary research plan that builds upon our preliminary data to
explore both the mechanism of CIPN and the degree to which FDA-approved drugs can be repurposed for the
treatment or prevention of the condition. In Aim 1, we will examine the influence of platinum-DNA adducts and
release of high mobility group box-1 (HMGB1) in rodents following exposure to oxaliplatin. In Aim 2, we will
investigate whether the receptor Toll-like receptor (TLR4) is responsible for the development or maintenance of
CIPN across time. Finally, in Aim 3, we will conduct a proof of concept assessment of the efficacy of FDA-approved 
antiepileptic drugs on both neuronal ion currents and CIPN behavioral characteristics. These proposed studies will provide new therapeutic targets which will likely alter the detrimental effects of oxaliplatin on sensory neurons.

## Key facts

- **NIH application ID:** 9957139
- **Project number:** 5R01NS102415-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** FLETCHER A WHITE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,476
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957139

## Citation

> US National Institutes of Health, RePORTER application 9957139, The role of cell-specific TLR-4 signaling in oxaliplatin-induced peripheral neuropathy (5R01NS102415-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9957139. Licensed CC0.

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