# Improving the translational value of head and neck cancer patient-in-mouse models

> **NIH NIH R37** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $71,347

## Abstract

Project Abstract:
 Patient-derived model systems are commonly used to study tumor biology and test novel treatments for
head and neck cancer. These models are established using patient tumors sourced from surgical specimens
and typically implanted into the subcutaneous tissue of the mouse. There is little data available to support the
decisions we make during the initial handling of the tumor samples and, most importantly, how these decisions
impact the results of subsequent studies. Our long-term goal is to improve outcomes for head and neck cancer
patients using valid, predictive, and well characterized model systems. The overall objective of this application
is to improve our use of these mammalian model systems by understanding the impact of choices we make
when we establish them. By combining innovative approaches to study cancer evolution with rigorous
assessment of tumor biology and therapy response we hope to ultimately improve the relevance of studies
using these mammalian models to improve the care of human patients. Our central hypothesis is that the
approach used to establish patient-derived xenografts has a critical impact on their relevance as translational
models.
 To achieve our goals, we proposed three aims. In Aim 1, we will determine the role of heterotopic vs.
orthotopic implantation on the biology of the tumor, how patient-derived animal models change with increasing
passage in animals, and how these factors impact tumor evolution. In Aim 2, we will test the concordance of
response between patient derived models and patients by using patient derived xenografts established as part
of an ongoing (and separately funded) window-of-opportunity trial and will assess consistency in response to
standard treatments over time. In Aim 3, we will use an innovative humanized mouse model developed at
Wisconsin to assess the evolutionary interplay between the tumor and immune system, understand whether
these novel mice replicate the tumor/immune interface seen in human cancers or in syngeneic HNC models,
and investigate how well the response to immunotherapy replicates that seen in patients. In summary, these
studies will provide compelling evidence for how to optimize our use of mouse models of human head and
neck cancer. Completion of this project will provide robust evidence delineating and refining best practices for
the translational use of patient derived xenograft animal models of head and neck cancer.

## Key facts

- **NIH application ID:** 10977490
- **Project number:** 3R37CA255330-04S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Randall J. Kimple
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $71,347
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977490

## Citation

> US National Institutes of Health, RePORTER application 10977490, Improving the translational value of head and neck cancer patient-in-mouse models (3R37CA255330-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10977490. Licensed CC0.

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