# Translational application of mouse models of melanoma brain metastases

> **NIH VA I01** · VA NEW JERSEY HEALTH CARE SYSTEM · 2022 · —

## Abstract

Much has been learned about the molecular pathology of melanoma in recent years and significant progress
has been made towards its treatment, yet late-stage melanoma still remains one of the least curable cancers
with high metastatic propensity. The brain is a common site of metastasis for patients with various neoplasia
including melanoma, breast cancer, lung cancer, and colorectal cancer. The mainstay for treatment of brain
metastasis has been radiation therapy; sometimes surgery and chemotherapeutic agents have been included.
Most clinical trials usually excluded patients with brain metastases because of the unlikelihood these patients
will benefit from such regiment, however, recently a few trials have included melanoma patients with or without
brain metastases. Preliminary results from these trials are suggestive that similar responsiveness was observed
for patients with or without brain metastases, and further trials are needed to confirm these results. Despite these
improvements, patients with multiple brain metastases from solid tumors often show progression in the brain
contributing to neurological deterioration, decreased quality of life, and poor survival.
Mouse models reflecting human cancers are important tools towards the translation of basic science discoveries
to clinical therapies. However, rapidly evolving technologies within the last few years require further refining
current approaches that enable models to be more suitable in robust translational applications to provide
consistent information to meet patients’ needs. In our studies of melanoma, we discovered that >65% of human
melanoma cell lines and melanoma biopsies express metabotropic glutamate receptor 1 (GRM1), independent
of N-RAS/B-RAF genotypes, while normal human melanocytes do not. Based on this discovery, our group was
the first to propose the link between GRM1-mediated glutamatergic signaling and melanoma. In recent clinical
trials, we observed that >90% of all enrolled patients expressed GRM1 within their late-stage melanomas.
However, the conventional mouse models of melanoma do not mimic this genetic alteration common to
melanoma patients. Therefore, we developed mouse models (MASS and TGS) where the ectopic expression of
GRM1 in previously normal melanocytes leads to consistent, wide-spread development of melanocytic lesions
and metastasis to various organs including the lung and brain, two common metastatic sites for human
melanoma. In this application, we propose to characterize the ability of these two different but complementary
innovative models that mimic human melanoma with brain metastases and fill the gap, to expand, improve, and
transform the utility of mammalian tumor models for translational research. Completion of this proposed work is
an essential step towards establishing fundamentally important and relevant animal models of human cancer
that will improve and save cancer patient lives.

## Key facts

- **NIH application ID:** 10371885
- **Project number:** 5I01BX003742-05
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Suzie Chen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371885

## Citation

> US National Institutes of Health, RePORTER application 10371885, Translational application of mouse models of melanoma brain metastases (5I01BX003742-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10371885. Licensed CC0.

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