# PQ12 Targeting HDAC6 for Chemotherapy-Induced Neuropathy and Chemobrain

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $366,766

## Abstract

SUMMARY
 Chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairment
(CICI) are major side effects of cancer treatment that frequently persist long into survivorship. No drugs have
been approved by the US Food and Drug Administration to prevent and/or adequately manage CIPN and CICI.
This application aims at filling this void. A concern when designing drugs to manage CIPN and CICI is that
they should not impair tumor control. Ideally, agents to control these neurotoxicities should also enhance
tumor control. Recent findings indicate that inhibitors of histone deacetylase 6 (HDAC6) meet these goals.
 HDAC6 de-acetylates non-histone cytosolic proteins like tubulin without inducing epigenetic changes.
Recent preclinical and clinical data show promise for HDAC6 inhibitors to improve tumor control. We
recently showed that HDAC6 inhibition fully reverses established CIPN in cisplatin-treated mice. This was
associated with restoration of mitochondrial health in sensory neurons. Preliminary data indicate that co-
administration of HDAC6 inhibitors protect against CIPN by preventing mitochondrial damage. Additional
preliminary data indicate that HDAC6 inhibition also reverses established CICI and associated brain
mitochondrial damage.
 Our hypothesis is that HDAC6 inhibition prevents and reverses CIPN and CICI in mice with or without
tumors by targeting mitochondrial health, oxidative stress, and downstream neuroimmune pathways. We will
test our hypothesis in 3 specific aims: Aim1: Determine the capacity of HDAC6 inhibitors to prevent CIPN in
mice with or without tumors. Aim 2: Determine the effect of HDAC6 inhibition on established CIPN. Aim 3:
Determine whether the beneficial effects of HDAC6 inhibition extend to CICI. In aims 1 and 3, we will
investigate the effect of HDAC6 inhibitors on tumor control and ensure that HDAC6 inhibitors also prevent
CIPN and CICI in the presence of a tumor.
 This study is innovative because we propose to target HDAC6 activity in neurons to control
neurotoxicities while at the same time enhancing cancer control. The expected outcome is significant because
it will identify HDAC6 inhibition as a realistic novel approach to control CIPN and CICI. This will increase the
quality of life of millions of cancer patients and survivors. Clinical trials to examine the effect of HDAC6
inhibitors on tumor control are already underway, and therefore the expected results of this project should
rapidly convince clinicians to examine the value of HDAC6 inhibitors for management of both CIPN and CICI.
Identification of HDAC6 inhibitors as drugs that can be used after completion of chemotherapy to completely
resolve established CIPN and CICI will be of great benefit for cancer survivors suffering every day from
these persistent neurotoxicities.

## Key facts

- **NIH application ID:** 9914096
- **Project number:** 5R01CA227064-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Cobi J Heijnen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,766
- **Award type:** 5
- **Project period:** 2018-05-22 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914096

## Citation

> US National Institutes of Health, RePORTER application 9914096, PQ12 Targeting HDAC6 for Chemotherapy-Induced Neuropathy and Chemobrain (5R01CA227064-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9914096. Licensed CC0.

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