# Project 1:  Defining and Targeting Pathways that Drive Head and Neck Cancer

> **NIH NIH P50** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $289,713

## Abstract

PROJECT SUMMARY
Head and neck cancer (HNC) is the sixth most common cancer in the United States. Today we know that this
cancer represents two distinct diseases, human papillomavirus positive (HPV+) HNC and HPV negative
(HPV-) HNC, with remarkably different molecular profiles and clinical outcomes. Yet, these two diseases are
currently treated the same way, using surgery combined with chemoradiotherapy that are commonly
associated with significant morbidities and modest overall survival rates for the HPV- cohort. Multiple genes
are mutated in HNC. Which of these mutated genes are the true drivers of carcinogenesis in the head and
neck, and under what context, is not known. Identifying these genes and exploring biomarkers predictive of
disease severity can be achieved using genetically engineered mice. In this project, we will make use of our
prior expertise in developing well-validated mouse models for human cancers to identify driver mutations in
HNC, and test drugs that target the molecular pathways impacted by these drive mutations. We will use
information gained from genome-wide analyses of these mouse models to identify biomarkers that are
predictive of disease severity and response to therapy, and test their utility in human HNCs making use of the
broad panel of patient derived xenografts (PDXs) recently established at the University of Wisconsin. This
project has three specific aims: (1) define mutations that drive head and neck carcinogenesis; (2) identify
therapeutic targets for treating HNC; and (3) perform human endpoint analyses using human HNC tissue
microarrays to identify biomarkers that are predictive of disease severity and response to therapy. This project
is highly innovative and significant because we shall identify mutations that drive HNC, test relevant new
targets for therapy and define new prognostic biomarkers for human HNC.

## Key facts

- **NIH application ID:** 9988234
- **Project number:** 5P50DE026787-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Paul F. Lambert
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $289,713
- **Award type:** 5
- **Project period:** 2016-08-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988234

## Citation

> US National Institutes of Health, RePORTER application 9988234, Project 1:  Defining and Targeting Pathways that Drive Head and Neck Cancer (5P50DE026787-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9988234. Licensed CC0.

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