# Wnt Signaling in the Development of Aggressive Thyroid Cancer

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $7,157

## Abstract

Project Summary
The incidence of thyroid cancer is rapidly increasing in the US and is projected to surpass colorectal cancer as
the 4th leading cancer diagnosis by 2030. The majority of patients respond to initial therapy, but approximately
20% will develop recurrence and 10% will develop metastatic disease. Treatment options are extremely limited
for patients with metastatic, recurrent, or poorly-differentiated disease, such as anaplastic thyroid carcinoma
(ATC). ATCs usually carry common driver mutations, such as BRAFV600E, but BRAF inhibitors have shown limited
efficacy in the treatment of ATC. Interestingly, the majority of ATC have also been found to exhibit increased
Wnt activity, and Wnt has been shown to mediate BRAF-inhibitor resistance in other cancer types. Wnt has also
been shown to contribute to aggressive tumor behavior through the development of an immunosuppressive
tumor microenvironment. The goal of my proposal is to define the role of Wnt in tumor progression and
therapeutic resistance in anaplastic thyroid cancer. My preliminary work in the development of novel spheroid
and organoid culture systems provides a unique opportunity to analyze the effects of Wnt inhibitors in a near-in
vivo system derived from primary patient samples. In this proposal, I will test the hypothesis that Wnt signaling
in the tumor and tumor microenvironment drive disease progression and therapeutic resistance in aggressive
thyroid cancers. In Aim 1, I will define the molecular interaction between the Wnt and MAPK signaling pathways
that enable resistance to BRAF inhibitors and examine the potential utility of Wnt inhibitors in the treatment of
BRAF-inhibitor resistant and aggressive disease. In Aim 2, I will elucidate the role of Wnt in the development of
an immunosuppressive tumor microenvironment and investigate the immunomodulatory properties of Wnt
inhibitors in vivo utilizing a humanized tumor xenograft murine model and in vitro using monocyte-tumor spheroid
co-cultures, both of which I have developed for this project. In completing these studies, I will delineate the
contributions of Wnt in BRAF-inhibitor resistance and immunomodulation in aggressive thyroid cancer in order
to characterize a therapeutic target in a disease with limited treatment options.

## Key facts

- **NIH application ID:** 10385266
- **Project number:** 1F31CA261060-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Kensey Bergdorf
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,157
- **Award type:** 1
- **Project period:** 2022-02-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385266

## Citation

> US National Institutes of Health, RePORTER application 10385266, Wnt Signaling in the Development of Aggressive Thyroid Cancer (1F31CA261060-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10385266. Licensed CC0.

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