# The Role of Abl Kinase Signaling in HER2+ Breast Cancer Brain Metastasis

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,394

## Abstract

Breast cancer brain metastasis (BCBM) occurs in approximately 50% of late-stage Human Epidermal Growth
Factor Receptor 2-positive (HER2+) breast cancer patients. BCBM may result in cognitive decline and cranial
neuropathies and is associated with a median survival rate of nine months. Current therapies for BCBM, such
as whole brain radiation therapy, can enhance cognitive impairment while targeted therapies and chemotherapy
are ineffective. Despite the increased patient survival due to HER2 targeted therapies, patients often relapse
due to brain metastases. Recently, our laboratory has discovered a role for Abelson (Abl) family of tyrosine
kinases, ABL1 and ABL2, in breast cancer bone metastasis and lung cancer brain metastasis. Evaluation of 279
HER2+ breast cancer patients demonstrates a correlation between high expression of ABL1 and decreased
distant metastasis free survival. My preliminary experiments have shown decreased brain colonization by HER2+
breast cancer cells when mice are treated with the allosteric Abl kinase inhibitor GNF5. I will evaluate the
hypothesis that HER2 signals through Abl kinases to promote HER2+ breast cancer metastasis to the brain. This
hypothesis will be tested in the following aims: (1) Identify the steps of the metastatic cascade that require Abl
kinase signaling. (2) Elucidate the mechanism of Abl signaling in brain metastatic HER2+ breast cancer cells.

## Key facts

- **NIH application ID:** 9830596
- **Project number:** 5F31CA224952-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Courtney Michelle McKernan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,394
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830596

## Citation

> US National Institutes of Health, RePORTER application 9830596, The Role of Abl Kinase Signaling in HER2+ Breast Cancer Brain Metastasis (5F31CA224952-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830596. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*