# Is ERBB4 a Driver of BRAF WT Melanomas?

> **NIH NIH R15** · AUBURN UNIVERSITY AT AUBURN · 2024 · $20,349

## Abstract

Combining immune checkpoint inhibitors with BRAF and MEK inhibitors has enabled
significant improvements in treating metastatic skin cutaneous melanomas that possess
activating mutations in the BRAF gene (“BRAF mutant melanomas”). In contrast, actionable
and specific targets in metastatic cutaneous melanomas that contain the wild-type BRAF gene
(“BRAF WT melanomas”) have yet to be discovered, hindering the development of more
effective strategies for treating these tumors. Here we propose to address that knowledge gap
by validating a candidate target in BRAF WT melanomas and strategies for therapeutic
intervention. Published and preliminary data have led to the following hypothesis: ERBB4
mutations or elevated ERBB4 transcription increase signaling by ERBB4-EGFR or ERBB4-
ERBB2 heterodimers, resulting in increased PI3 kinase signaling, cooperation with NF1 or
RAS gene mutations, and increased proliferation of BRAF WT melanomas. We will test
aspects of this hypothesis with two specific aims: (1) Which ERBB4 mutants found in BRAF
WT melanomas cause increased proliferation of BRAF WT melanoma cell lines? (2) Is
EGFR, ERBB2, or the PI3K pathway required for proliferation of the ERBB4-dependent,
BRAF-WT melanoma cell lines? We estimate that the predicted outcome of these studies will
lead to effective strategies for treating approximately 30% of metastatic BRAF WT
melanomas, revolutionizing the care of patients that carry these aggressive skin cancers.

## Key facts

- **NIH application ID:** 11064642
- **Project number:** 3R15CA280767-01A1S1
- **Recipient organization:** AUBURN UNIVERSITY AT AUBURN
- **Principal Investigator:** David J. Riese
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $20,349
- **Award type:** 3
- **Project period:** 2024-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11064642

## Citation

> US National Institutes of Health, RePORTER application 11064642, Is ERBB4 a Driver of BRAF WT Melanomas? (3R15CA280767-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11064642. Licensed CC0.

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