# Employing Novel Primary Mouse Models of Head and Neck Cancer to Overcome Chemoradiation Resistance

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $160,812

## Abstract

Head and neck cancer poses significant treatment challenges due to high rates of recurrence after definitive
therapy for locally advanced disease. Radiation therapy with concurrent cisplatin has been the standard of care
for non-surgical management of head and neck cancer for the past 15 years, with no recent therapeutic
advances to improve outcomes for head and neck cancer that is unrelated to human papillomavirus (HPV)
infection. Preclinical models of HPV-negative head and neck cancer are critical to improve the understanding
of the biology of these tumors to devise novel treatment strategies. Most currently available preclinical head
and neck cancer models utilize xenografts in immunodeficient mice or syngeneic transplant tumor models,
which have limited tumor heterogeneity and do not recapitulate gradual co-evolution of human tumors with an
intact immune system. This lack of preclinical models that mimic human head and neck cancer development
and metastasis represents a substantial barrier to studying tumor biology and discovering effective new
therapies for this disease. To address this gap, the current proposal employs novel spatially and temporally
restricted carcinogen-induced and genetically engineered mouse models of head and neck squamous cell
carcinoma in immunocompetent mice to interrogate mechanisms of chemoradiation resistance and to assess
novel therapeutic combinations with radiation therapy. The long-term goal of this research is to identify and test
new approaches to improve radiation response and to reduce development of metastatic disease for head and
neck cancer patients. In preparation for launching a successful independent research program, receipt of a
K08 Award will facilitate credentialing these novel primary preclinical tumor models. Moreover, a K08 Award
will provide the opportunity to acquire new knowledge and skill sets to study genetic alterations and epigenetic
changes affecting tumor response and resistance to therapy. In addition, it will facilitate protected time for
focused training in grant writing, laboratory management, and career development. The proposed research is
innovative because it employs the first preclinical models with spatially and temporally restricted tumors
induced by genetic mutations that are commonly identified in human head and neck cancer, along with
exposure to a clinically relevant carcinogen present in tobacco. These novel models will be used to test the
hypothesis that targeting the ATR DNA damage response pathway and programmed cell death protein 1 (PD-
1) immune checkpoint with concomitant radiation therapy will improve local and distant control of head and
neck cancer. This research will establish a preclinical platform for improving understanding of head and neck
cancer biology and for evaluating new therapeutic combinations with radiation therapy for this difficult to treat
disease.

## Key facts

- **NIH application ID:** 10925397
- **Project number:** 5K08DE029887-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yvonne MARIE Mowery
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $160,812
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925397

## Citation

> US National Institutes of Health, RePORTER application 10925397, Employing Novel Primary Mouse Models of Head and Neck Cancer to Overcome Chemoradiation Resistance (5K08DE029887-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10925397. Licensed CC0.

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