# Targeted EGFR for basal subtype pancreatic cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $639,879

## Abstract

Abstract
We and others have shown that basal tumors, which comprise <20% of PDAC tumors, are resistant to the first-
line chemotherapy regimen FOLFIRINOX. We show that basal tumors are significantly enriched in receptor
tyrosine kinases, including EGFR. While EGFR inhibitors have been consistently disappointing in PDAC, our
analysis of two clinical trials where patients were treated with gemcitabine in combination with an EGFR
inhibitor, shows that the negative results are very likely driven by the previous lack of knowledge of subtypes.
In both clinical trials, patients with basal tumors significantly benefit from EGFR inhibitor treatment. It is
noteworthy that the survival of patients with basal subtype tumors is significantly worse than patients with
classical tumors. We show that, for the very first time, basal patients who receive anti-EGFR therapy benefit
from EGFR inhibitor therapy (patients with classical subtype tumors do not), and can achieve equivalent
outcome to classical patients. Our findings strongly support that the positive subgroup analysis of basal
patients is explained by the higher EGFR kinase expression found in basal tumors. These data strongly
support our hypothesis that targeting subtype-specific kinases will be key to promising precision oncology
approaches for kinase inhibitors in PDAC. We propose a multi-disciplinary team of a translational researcher
(Yeh), kinome expert (Johnson), and medical oncologist (Somasundaram), that takes the next step in
determining if EGFR inhibitors should be repurposed for patients with basal subtype tumors, and leverages a
transformative high sensitivity method of defining the kinome in low input samples such as biopsies, to identify
targeted approaches specifically for basal subtype tumors.

## Key facts

- **NIH application ID:** 10826126
- **Project number:** 1R01CA288145-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** GARY L. JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $639,879
- **Award type:** 1
- **Project period:** 2024-02-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826126

## Citation

> US National Institutes of Health, RePORTER application 10826126, Targeted EGFR for basal subtype pancreatic cancer (1R01CA288145-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10826126. Licensed CC0.

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