# CCL2 and CCR2 as metastatic drivers and therapeutic targets in medulloblastoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $772,874

## Abstract

PROJECT SUMMARY
Brain tumors are the most common solid tumor and the leading cause of cancer-related death in children.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Dissemination (metastasis) of MB
results in seeding the leptomeningeal membranes that cover the brain and spinal cord. The unique pattern of
dissemination leads to a relatively non-empirically supported model in which medulloblastoma was assumed to
spread through passive shedding of cells into the cerebrospinal fluid, followed by distal implantation on the
surface of the nervous system. We have now demonstrated experimentally, that medulloblastoma in fact
disseminates through the blood circulation just like every other known type of human cancer, with
hematogenously disseminated circulating tumor cells (CTCs) re-homing to the leptomeningeal compartment of
the nervous system. CTCs reseed the leptomeninges almost exclusively, only rarely seeding organs outside the
central nervous system. Hematogenous dissemination of medulloblastoma is an exciting development that offers
the chance for novel approaches to the diagnosis, prevention, and treatment of metastatic medulloblastoma.
The vast majority of medulloblastoma patients experience a `metastasis free' interval by imaging before their
metastatic recurrence, which may offer a window to prevent metastatic recurrence. In patients with established
metastatic disease, identifying the genes enabling CTCs to drive metastases could prevent or ameliorate disease
progression, offering novel diagnostic and therapeutic opportunities for medulloblastoma patients. Therefore we
will:
Aim 1). Isolate and analyze circulating tumor cells from humans and mice with MB to determine the utility of
 CCL2 and CCR2 as biomarkers for the development of metastases within distinct MB subgroups.
Aim 2). Manipulate CCL2/CCR2 expression using genetic/cell biology techniques to determine the contribution
 of each to MB metastasis in human xenograft and genetically modified mouse models that recapitulate distinct
 MB subgroups.
Aim 3). Use established FDA approved drugs and antibodies, as well as emerging drugs and tool compounds,
 to block CCL2/CCR2, individually, together, and in combination with chemotherapy and craniospinal radiation
 in mouse models, to determine if we can prevent, and/or treat the dissemination of MB preclinically.
There are no drugs or therapies for medulloblastoma metastases, despite the fact that metastases are the
overwhelming cause of death, and the major source of long-term morbidity. We present a series of experiments
that clarify how brain tumors can spread hematogenously, identify markers to improve diagnosis, and develop
therapies applicable in near term to the treatment of metastatic MB in children.

## Key facts

- **NIH application ID:** 10320941
- **Project number:** 5R01CA255369-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Livia Garzia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $772,874
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320941

## Citation

> US National Institutes of Health, RePORTER application 10320941, CCL2 and CCR2 as metastatic drivers and therapeutic targets in medulloblastoma (5R01CA255369-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320941. Licensed CC0.

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