# Mechanisms of neuroinflammation in brain metastasis progression

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2021 · $373,843

## Abstract

Project Summary
Title: Mechanisms of neuroinflammation in brain metastasis progression
 Despite significant progress in early cancer screening and treatment regimens for primary tumors, the
overall mortality of patients with metastatic relapse has not improved in the past two decades. Many sites of
metastatic relapse are commonly diagnosed in the clinic, but brain metastasis is the most devastating with a
median survival of fewer than six months. Thriving in a "sanctuary" protected by the blood-brain barrier (BBB),
brain metastases are shielded from most anti-cancer drugs. As a result, the incidence of brain metastasis is
increasing, despite increasing control of primary tumors. Thus, to reduce cancer mortality, rationally designed
therapeutics, based on a mechanistic understanding of metastasis in the context of the unique brain
microenvironment, are urgently needed for brain metastasis patients. The immune system has indisputable
and ubiquitous roles in regulating both primary tumors and metastases. Traditionally viewed as
immunoprivileged organ, the role of neuroinflammation in brain tumor progression is largely underexplored. In
this proposed study, we will use transgenic mouse models and state-of-the-art genomics and imaging
approach to trace and analyze the role of highly heterogeneous cell types involved in neuroinflammation and
their roles in regulating brain metastatic outgrowth. This collaborative effort from a multidisciplinary team,
including a cancer biologist, an expert in neuroinflammation, a computational biologist and a bioinformatician
and will allow us to: 1) dissect distinct contribution subpopulation of myeloid cells in regulating brain metastasis
at phenotypical level (Aim 1); 2) visualize and quantitatively measure the behavior of brain microenvironmental
niche and transcriptome heterogeneity of inflammatory myeloid cell that that nurtures metastasis in brain (Aim
2). 3) Targeting pro-inflammatory myeloid cells as means of brain metastasis prevention. Shifting the current
clinical treatment model relies on new in-depth mechanistic insights obtained through basic and pre-clinical
innovative research. Utilizing cutting-edge sequencing and imaging modality coupled with classic transgenetic
models and clinical tissue samples, we now have the unprecedented capacity to systematically dissect the
traits of metastatic behavior and discover potential novel therapeutic targets for paradigm-shifting novel
adjuvant therapy for brain metastasis patients.

## Key facts

- **NIH application ID:** 10201524
- **Project number:** 5R01CA222405-04
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Siyuan Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,843
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201524

## Citation

> US National Institutes of Health, RePORTER application 10201524, Mechanisms of neuroinflammation in brain metastasis progression (5R01CA222405-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201524. Licensed CC0.

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