# AN IMAGING-BASED APPROACH TO UNDERSTAND AND PREDICT CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $375,524

## Abstract

PROJECT SUMMARY
Cancer survival rates are increasing dramatically as novel early diagnostics and new treatments emerge.
However, there is a great cost in the form of acute and chronic pain that chemotherapy patients experience
immediately after and for many years following successful treatment. As chemotherapy drugs travel throughout
the body to target and destroy cancer cells, they severely damage other organs, including nerves, leading to a
condition known as chemotherapy-induced peripheral neuropathy (CIPN). Symptoms often appear minutes to
hours after the treatment and include pain in the arms and hands, burning or tingling, loss of sensation to touch,
difficulties in performing common routines, cramping, constipation, muscle weakness, and balance problems.
The search for a treatment for CIPN is one of the major challenges in current oncology practice, with the
identification of new agents to prevent and/or treat CIPN being a top priority and long-term objective.
Unfortunately, no methods are currently available to assess the extent of CIPN or predict outcomes. Identification
of specific biological mechanisms underlying the manifestation of painful CIPN requires a diagnostic tool to
monitor CIPN in living subjects to identify a potential therapeutic target. It has been proposed that damaging
radicals known as reactive oxygen and nitrogen species (ROS/RNS) cause nerve tissue injury and play a critical
role in neurodegenerative diseases. To test this mechanism in living animals, we propose to investigate the
spatial, temporal, and interventional aspects of the ROS response to chemotherapy in CIPN animal models and
correlate the in vivo imaging results with disease progression. We will be focusing on the mechanism that is
related to the burst of ROS, and the repetitive damage in the nerve tissue assessed by the proposed selected
markers of chronic CIPN. In the Aim 1 we will first demonstrate that the repetitive stimulation of ROS pathway in
mice leads to the symptoms associated with CIPN. After establishing this link, will demonstrate in Aim 2 that the
other chemotherapy drugs such as paclitaxel and bortezomib that act with different cytotoxic mechanisms but
show similar CIPN behavior follow the same mechanistic pathway. Finally, in Aim 3 we will test our hypothesis
in syngeneic and patient-derived xenograft breast cancer models by demonstrating that pharmacological
intervention using FDA-approved drugs will minimize ROS and chronic CIPN while not undercutting treatment
efficacy. This strategy of combined imaging, histological, biochemical and behavioral methods will lead to
identification of the molecular roots of chronic pain in living animals, providing mechanistic insight into the
pathogenesis of CIPN. Overall, the outline proposal will enable us to correlate the acute form with chronic CIPN
and explore several image-guided strategies to minimize CIPN.

## Key facts

- **NIH application ID:** 9983642
- **Project number:** 5R01CA208623-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Mikhail Y. Berezin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,524
- **Award type:** 5
- **Project period:** 2017-08-16 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983642

## Citation

> US National Institutes of Health, RePORTER application 9983642, AN IMAGING-BASED APPROACH TO UNDERSTAND AND PREDICT CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY (5R01CA208623-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983642. Licensed CC0.

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