# PKCdelta and salivary gland radioprotection

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $481,884

## Abstract

ABSTRACT
Over 50,000 people a year are diagnosed with head and neck cancer (HNC) in the US, the majority of whom
will be treated with δ-irradiation (IR) therapy. Many of these patients will experience debilitating side effects as
a consequence of IR damage to non-tumor tissues, including the oral mucosa, tongue and salivary glands. In
particular, destruction of the salivary glands, and resultant hypofunction, is permanent and associated with
chronic oral infections, caries, and severe discomfort. Early loss of salivary gland function is thought to result
from direct damage to salivary acinar cells by IR and the subsequent loss of cells through apoptosis, while
permanent loss of function likely results from the inability of the IR damaged gland to regenerate cells lost
through apoptosis. Our long-term goal is to understand how protein kinase C delta (PKCδ) regulates the
response of the salivary gland to IR, so as to develop better strategies for radioprotection. Our studies show
that inhibition of PKCδ activation using tyrosine kinase inhibitors (TKIs) suppresses apoptosis and provides
robust radioprotection in mouse models of head and neck IR. However, very little is known about the
mechanisms by which PKCδ regulates DNA damage induced apoptosis, and conversely, how inhibition of
PKCδ provides radioprotection. In Aims 1 and 2 of this proposal, we will explore the hypothesis that inhibition
of PKCδ suppresses apoptosis and protects against the initial, or “early” effects of IR damage to the salivary
gland through regulation of the DNA damage response and increased DNA repair. In addition to suppressing
apoptosis, our preliminary data suggests that TKIs can provide long term radioprotection of salivary gland by
promoting salivary acinar cell regeneration in vivo. In Aim 3 we will explore the hypothesis that TKIs promote
regeneration of salivary acinar cells, and establish whether genetic disruption of PKCδ provides long term
radioprotection though a similar mechanism. Our studies will define the mechanism(s) underlying
radioprotection of the salivary gland by inhibition of PKCδ and TKIs, and may lead to the identification of new
“rational” strategies for radioprotection for oral tissues. Although our focus is on the salivary gland, such
strategies may also have implications for protection of other non-tumor tissues in patients undergoing IR and
possibility chemotherapy, thus having a significant impact on the quality of life and efficacy of therapeutic
interventions for a wide variety of cancer patients.

## Key facts

- **NIH application ID:** 10190894
- **Project number:** 5R01DE027517-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MARY ELAINE REYLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,884
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190894

## Citation

> US National Institutes of Health, RePORTER application 10190894, PKCdelta and salivary gland radioprotection (5R01DE027517-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190894. Licensed CC0.

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