# Identification of Epigenetic Regulators Mediating Resistance to FGFR Inhibition in Squamous Cell Carcinoma

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $185,491

## Abstract

PROJECT SUMMARY/ABSTRACT
Squamous Cell Carcinoma (SCC) is a common cancer that develops in stratified epithelial tissues such as the
epidermis, the oral cavity, and the lungs. Standard treatments for patients with un-resectable SCC, which
include radiation, cis-platin, 5-fluorouracil, and paclitaxel, are only modestly effective, resulting in approximately
45,000 deaths every year. While there has been some progress in the development of target therapies, such
as EGFR inhibition, these treatments have not shown the efficacy seen in other tumors such as lung
Adenocarcinoma. Recent advances in immunotherapy have shown great promise in treating SCC, even at
advanced stage, but like many other tumor types only a minority of SCC patients respond to immunotherapy.
In addition, the risk of cutaneous SCC is greatly increased in immunosuppressed transplant recipients, who are
poor candidates for immunotherapy. This project aims to identify novel therapeutic targets that mediate
resistance to FGFR inhibition in SCC. We will employ an orthotopic transplant model system that is driven by
genetic alterations commonly found in human SCC tumors. A drop-out screen using a CRISPR/Cas9 library
will be performed in vivo using orthotopic tumors. Hits will be validated using in vitro and in vivo SCC model
systems employing either shRNA or CRISPR/Cas9-based target gene knockdown, as well as available
antibody-based or small molecule inhibitors. In addition, we will validate the expression of potential targets
human SCC tumors by Tissue Microarray, which will help to identify clinical characteristics of patients that may
benefit from this therapeutic strategy. There are many drugs that are FDA-approved or in clinical trials that
have not been tested for cooperation with FGFR inhibition, and thus this un-biased approach is likely to
uncover unexpected vulnerabilities that can be rapidly translated into treatments for SCC patients.

## Key facts

- **NIH application ID:** 9870895
- **Project number:** 5R21CA226099-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Matthew Robert Ramsey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,491
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870895

## Citation

> US National Institutes of Health, RePORTER application 9870895, Identification of Epigenetic Regulators Mediating Resistance to FGFR Inhibition in Squamous Cell Carcinoma (5R21CA226099-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870895. Licensed CC0.

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