# Inflammation and EGFR crosstalk in HNSCC Therapy

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $353,763

## Abstract

Project Summary
Given the importance of oncogenic epidermal growth factor receptor (EGFR) signaling for tumor cell
proliferation in head and neck squamous cell carcinoma (HNSCC), we believe that EGFR inhibition remains
worthy as a strategy to be included in radiotherapy (RT) protocols for HNSCC and that further investigation of
mechanisms responsible for poor response to EGFRIs is warranted. Based on our preliminary data, we propose
that increased interleukin-1 (IL-1) signaling may lead to sustained interleukin-8 (IL-8) signaling and NADPH
oxidase 2 (NOX2)-derived superoxide (O2.-) production which is associated with pro-survival signaling and an
immunosuppressive tumor microenvironment leading to poor response to EGFRIs. As a result, targeting the
IL-1 signaling pathway may enhance HNSCC tumor response to EGFRIs combined with RT. The overall
hypothesis of this grant application is that NOX2 redox activity and IL-8 signaling contribute to poor long-term
anti-tumor response to EGFRIs via increased IL-1 signaling in RT-treated HNSCC tumors. Aim 1 will
determine if IL-1-mediated NOX2 redox activity is involved in poor HNSCC tumor response to RT+EGFRIs;
Aim 2 will determine if IL-1-mediated IL-8 signaling is involved in poor HNSCC tumor response to
RT+EGFRIs; and Aim 3 will determine if inhibition of IL-1 signaling would enhance HNSCC tumor response to
RT+EGFRIs. Overall, we expect that this application will highlight novel redox mechanisms associated with
poor response to EGFRIs and possibly lead to promising new therapeutic approaches for RT-treated HNSCC
patients.

## Key facts

- **NIH application ID:** 11069514
- **Project number:** 1R01DE033695-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Andrean Llewela Burnett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $353,763
- **Award type:** 1
- **Project period:** 2024-09-05 → 2025-06-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11069514

## Citation

> US National Institutes of Health, RePORTER application 11069514, Inflammation and EGFR crosstalk in HNSCC Therapy (1R01DE033695-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11069514. Licensed CC0.

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