# Investigating the Role of the Tumor MicroEnvironment in Resistance of Urothelial Carcinoma of the Bladder to FGFR3 Inhibition

> **NIH NIH F30** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $33,650

## Abstract

Project Summary
 Urothelial carcinoma of the bladder (i.e. bladder cancer) is the most common primary tumor of the
urothelial tract. Bladder cancer recurrence and metastases remain common and are significant contributors to
patient morbidity and mortality. Despite the high prevalence of recurrence and metastasis, no new treatment
options have been introduced for advanced disease in the past three decades. Many patients who initially
respond to standard of care treatment exhibit refractory disease within a few years. Furthermore, patients with
metastatic disease at the time of diagnosis often exhibit resistance to standard of care therapeutic treatment.
These cases underscore the urgent need for new therapies. One potential target for new therapy is fibroblast
growth factor receptor 3 (FGFR3), which is frequently mutated in bladder cancer. In vitro studies with FGFR3
inhibitors showed promising results, however, the in vivo responses were more modest. Currently, it is
unknown what modulates response to FGFR3 inhibition in vivo, but I hypothesize that the microenvironment is
contributing to resistance mechanisms in bladder cancer.
 The goal of this proposal is to better understand the roles that the tumor microenvironment plays in
resistance of bladder cancers to Fibroblast Growth Factor Receptor 3 (FGFR3) inhibition. The overall
hypothesis is that constituents of the tumor microenvironment confer resistance to FGFR3 inhibition and
promote metastasis in bladder cancer, and that response may depend on cellular differentiation state. This
hypothesis will be tested by employing MicroEnvironment MicroArrays (MEMA), which consists of robotically
printed growth pads made up of combinations of functional extracellular matrix (ECM) components, growth
factors and cytokines found in different local and metastatic microenvironments, allowing for systematic
assessment of microenvironment effects on cellular phenotypes in a rational reductionist manner. Based on
preliminary data, the specific aims of this proposal are as follows: (1) Determine the role that the
microenvironment plays in resistance to FGFR3 inhibition in bladder cancer, and (2) Investigate the role that
the microenvironment plays in expression of differentiation state markers in response to FGFR3 inhibition in
bladder cancer. Results from this proposal have the potential to provide new information that will enable us to
devise novel targeted approaches aimed at anticipating or overcoming resistance to FGFR3 inhibition and
preventing metastases in this disease. Thus, this project has the potential to greatly impact bladder cancer
patients' quality of life and overall survival.

## Key facts

- **NIH application ID:** 9856141
- **Project number:** 5F30CA206333-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Cheryl Claunch
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,650
- **Award type:** 5
- **Project period:** 2017-02-01 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856141

## Citation

> US National Institutes of Health, RePORTER application 9856141, Investigating the Role of the Tumor MicroEnvironment in Resistance of Urothelial Carcinoma of the Bladder to FGFR3 Inhibition (5F30CA206333-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856141. Licensed CC0.

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