# Axonal transport and chemotherapy induced peripheral neuropathy

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2022 · $590,280

## Abstract

ABSTRACT
Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating sequela for many cancer
patients. For some patients this complication prevents optimal therapy and so jeopardizes the chance for a
cure, while many patients develop permanent, untreatable pain and severe sensory deficits that seriously
compromise quality of life for cancer patients and survivors. The mechanisms that cause axon degeneration
and sensory symptoms in CIPN are just beginning to be defined, and it is not yet clear whether the
mechanisms that underlie CIPN can be biologically resolved from anti-neoplastic efficacy of chemotherapy.
Against this backdrop, our previous studies under this grant have demonstrated a central role for increased
axonal Ca+2 and activation of Ca+2-dependent calpain proteases in CIPN. Building on these findings we will
identify the processes linking together 1) the direct effects of paclitaxel or other chemotherapies on
microtubules, 2) activation of molecules implicated in axon destruction, plus the loss of compounds that
promote axon survival and 3) opening of Ca+2 channels located within the long axons. Our studies make use
of rodent sensory neurons in compartmented cultures, immunocompetent mice with paclitaxel-sensitive breast
cancer, and new human iPSC-derived sensory neuron cultures prepared from patients with severe CIPN or
from patients resistant to CIPN. Using these innovative approaches we will identify therapeutic targets for
treating CIPN without compromising the anti-neoplastic efficacy of paclitaxel and we will develop novel
therapeutic compounds. Since the process of axon degeneration in CIPN is similar to that seen in diseases
including hereditary neuropathy, ALS, and Alzheimer’s disease, our insights and therapeutic approaches will
advance treatment for many additional debilitating diseases.

## Key facts

- **NIH application ID:** 10522882
- **Project number:** 2R01CA205255-06A1
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** ROSALIND A. SEGAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $590,280
- **Award type:** 2
- **Project period:** 2016-04-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522882

## Citation

> US National Institutes of Health, RePORTER application 10522882, Axonal transport and chemotherapy induced peripheral neuropathy (2R01CA205255-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522882. Licensed CC0.

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