Childhood Cancer

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The influence of the raphe nucleus and serotonin on progression of diffuse intrinsic pontine glioma

Institution: 
Board of Trustees of the Leland Stanford Junior University
Researcher(s): 
Richard Drexler, MD/PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
2024
Type of Childhood Cancer: 
Brain Tumors, Diffuse Intrinsic Pontine Glioma (DIPG)
Project Description: 

Recently, researchers discovered that interaction between a special type of brain cells (neurons) and cancer cells plays a crucial role in the growth and progression of a highly aggressive brainstem tumor in children called diffuse intrinsic pontine glioma (DIPG). The neurons associated with cancer cells contribute to tumor growth through direct electrical communication and signaling with chemicals like neurotransmitters (e.g., glutamate and GABA). While the importance of some neurotransmitters is known, the role of a different neurotransmitter "serotonin" remains unclear. This is extremely interesting because the neurotransmitter "serotonin" is widely present in the brain and leads us to question which role serotonin plays in the communication between cancer cells and healthy brain cells in the context of DIPG. One specific area of focus is the raphe nucleus, which contains the highest number of serotonin neurons in the brain and is located in the brainstem, in close relationship to the origin of DIPG. Serotonin neurons, which produce serotonin, are known for their important roles in conditions like epilepsy, anxiety, and depression. Understanding how serotonin and these serotonin neurons are involved in DIPG could provide insights into both the tumor's aggressiveness and its impact on the mental health of children with DIPG.

Project Goal:

Our project aims to figure out how the neurotransmitter serotonin and serotonin neurons are involved in DIPG. We want to find answers about how the serotonin system affects the tumor's aggressiveness and the decline in mental health in children with DIPG. To study this, we will perform several experiments using models of DIPG in animals and tissue cultures, along with new constructs specifically focused on serotonin. A crucial part of our project involves activating serotonin neurons in a specific part of the brain (the so-called raphe nucleus) to see how DIPG cells respond. These experiments will help us understand which serotonin neurons interact with cancer cells and how other brain cells are involved in these interactions. We will also explore the possibility of using drugs to influence serotonin neuronal activity, with the hope of reducing the aggressiveness of DIPG and improving mental health. We strongly believe that our research could change how we understand the role of neurotransmitters in DIPG and potentially reveal new ways to treat and cure this disease.