# Elucidating the protective role of stromal fibrosis to radiation-induced tumor immunity

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2020 · $31,446

## Abstract

PROJECT SUMMARY
Pancreatic Ductal Adenocarcinoma (PDAC) is one the most lethal cancers with a 5-year survival rate of 8%.
Current therapeutic options that successfully treat other cancers, including radiation therapy (RT), are only
minimally effective in PDAC. This recalcitrant nature of PDAC has been linked in part to its unique tumor
microenvironment (TME), which is mainly composed of collagen-rich extracellular matrix and abundant cancer
associated fibroblasts. Combined chemoradiotherapy strategies currently used against PDAC are ineffective at
generating sufficient tumor regression needed to achieve resectability. This lack of effective treatment options
highlights an emergent need to understand how the fibrotic nature of PDAC determines RT efficacy and RT-
induced tumor immunity. Our group recently demonstrated that Focal Adhesion Kinase (FAK), a cytoplasmic
protein tyrosine kinase hyperactivated in many cancers, plays a role in regulating tumor stromal fibrosis. FAK
inhibition was shown to reduce fibrosis and alter the desmoplastic stroma in PDAC, rendering it more responsive
to immunotherapies. My preliminary data shows that modulating the PDAC fibrotic stroma using FAK inhibitor
can increase the sensitivity of PDAC to radiotherapy both in vitro and in vivo. Thus, I hypothesize that the fibrotic
stroma contributes to PDAC resistance to RT and RT-induced tumor immunity. To test this hypothesis, we
aim to determine: 1) how RT shapes the PDAC TME, 2) the mechanism(s) by which inhibition of FAK signaling
improves RT efficacy, and 3) whether stromal disruption by FAK inhibition enhances RT-induced anti-tumor
immunity and response to checkpoint immunotherapy. The proposed study will not only help us understand how
different RT regimens shape the unique PDAC fibrotic stroma and how this fibrosis impacts RT efficacy, but also
inform us on how to best integrate fibrosis-depleting agents, such as FAK inhibitor, to improve RT efficacy in
PDAC. We hope that this study will eventually translate into clinical trials with the potential to directly benefit
PDAC patients.

## Key facts

- **NIH application ID:** 9984148
- **Project number:** 5F30CA243233-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Varintra Edlyn Lander
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,446
- **Award type:** 5
- **Project period:** 2019-07-09 → 2023-07-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984148

## Citation

> US National Institutes of Health, RePORTER application 9984148, Elucidating the protective role of stromal fibrosis to radiation-induced tumor immunity (5F30CA243233-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984148. Licensed CC0.

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