# MAPK pathway modulation in thyroid tumorigenesis

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $402,600

## Abstract

PROJECT SUMMARY/ABSTRACT
Thyroid cancer is the most common endocrine malignancy and incidences are rising. Thyroid cancers of
follicular cell origin stand out among solid tumors because many of the tumor-initiating genetic events are
known. Activating mutations of effectors of the MAPK signaling pathway are associated with both follicular and
papillary thyroid cancer, and occur throughout the spectrum of thyroid diseases from benign adenomas
through therapeutically refractive poorly-differentiated disease. Despite sharing activation of the MAPK
pathway, activation via different effectors in the pathway results in distinct and unique pathological outcomes,
including metastasis to distinct distant sites. We do not understand how activation of a single pathway via
different mutations within the signaling cascade results in different pathological outcomes and recruitment of
different tumor microenvironments. This paradigm is seen not only in thyroid cancer, but in other
malignancies. We will utilize recently generated mouse models of thyroid cancer to model follicular and
papillary thyroid cancers to study how activation of the oncogene Hras versus Braf affects tumor development
and can modify the tumor microenvironment. We hypothesize that mode of activation contributes to stromal
recruitment and extracellular matrix (ECM) modification, thus contributing to the pathobiology of tumor
formation and progression. The data generated in these studies will provide a better understanding of the
mechanisms by which different oncogenic events that activate the same pathway predisposes the
development distinct pathological outcomes. We hope to use these data to develop novel therapeutic and
prevention strategies for thyroid cancer.

## Key facts

- **NIH application ID:** 10074754
- **Project number:** 7R01CA214511-03
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Aime T. Franco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,600
- **Award type:** 7
- **Project period:** 2018-07-03 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074754

## Citation

> US National Institutes of Health, RePORTER application 10074754, MAPK pathway modulation in thyroid tumorigenesis (7R01CA214511-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10074754. Licensed CC0.

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