# Strategic inhibition of EGFR-family signaling using novel peptidomimetic inhibitors of HER-2 for the treatment of osteosarcoma

> **NIH NIH P20** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2021 · $221,415

## Abstract

Summary Osteosarcoma (PI: Sita Withers, PhD).
This proposal will identify novel treatment strategies for osteosarcoma which has a 5-year survival rate of 70%.
The expression of epidermal growth factor receptor HER2 is upregulated in 40% of human and canine
osteosarcomas and has correlated with a poor outcome in some human studies. Using murine models of
osteosarcoma and lung metastasis, Dr. Withers will evaluate EGFR:HER2 inhibitors of signaling pathways (eg,
PI3K-Akt and ERK/MAPK) that have shown efficacy in a xenograft mouse model of breast cancer. The
hypothesis of this proposal is that peptidomimetic HER2 heterodimerization inhibitors of EGFR-family
signaling will lead to novel tools for treating metastatic OSA. Dr. Withers' approach includes evaluation in a
naturally-occurring canine osteosarcoma model, which mimics more closely lung metastasis in humans, for
translational information in the treatment of human osteosarcoma. Combinations of small molecule inhibitors
will be identified which show in vivo efficacy against the development of osteosarcoma and also limit
metastasis to the lungs. 3D printing of osteosarcoma and immune cells will be used to characterize the effects of
HER2 inhibition in the context of exposure to typical features of the tumor microenvironment. Two specific
aims are proposed: Aim 1 To define the effects of EGFR-family signaling inhibition on OSA cell function and
signaling pathways. Aim 2 To detail the efficacy and toxicity of optimal EGFR signaling inhibition in
preclinical in vivo models of OSA.

## Key facts

- **NIH application ID:** 10104816
- **Project number:** 1P20GM135000-01A1
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Sita Withers
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $221,415
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104816

## Citation

> US National Institutes of Health, RePORTER application 10104816, Strategic inhibition of EGFR-family signaling using novel peptidomimetic inhibitors of HER-2 for the treatment of osteosarcoma (1P20GM135000-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104816. Licensed CC0.

---

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