Research And Grants

CXCR1/2 Signaling Pathway: A Role in the Invasive Mechanism of DIPG

High-grade gliomas (HGGs) make up 8-10% of children's brain tumors and are often fatal within two years. These tumors can develop in the cerebral cortex or infratentorial regions like the brainstem. About half of pediatric HGGs occur in midline locations such as the pons, known as diffuse midline gliomas (DMGs), including DIPGs. High-grade gliomas show distinct patterns, with DIPGs typically developing in mid-childhood. DIPGs are highly invasive, making understanding what drives this process to create effective treatments essential.

Our research has shown that, unlike cortical HGGs, DIPGs grow and spread more when implanted into brainstem tissue compared to cortical tissue. Additionally, brainstem microglia (support cells in the brain) enhance the growth and spread of brainstem tumors more than cortical microglia do. This indicates that specific factors in the brainstem environment support DIPGs.

We have identified several genes that are differently expressed between the brainstem and cortical microglia, including CXCL5. This gene is part of the CXCL-ELR+ family, which interacts with the CXCR1/2 receptors and is known to influence cell movement and cancer cell invasion, including in gliomas. Our initial findings suggest that the CXCR1/2 pathway may play a role in DIPG invasion.

With this grant, we aim to test how the CXCR1/2 pathway and related factors contribute to DIPG growth and spread. We will also evaluate whether the key players in this pathway could be potential targets for new DIPG treatments.

Our ultimate goal is to translate these findings into clinical trials, offering new hope to children and families affected by this devastating disease. By supporting our research, you are contributing to the development of targeted therapies that could revolutionize the treatment landscape for DIPG.