Targeting oncoregulon-licensed neuron-tumor interaction in medulloblastoma
Medulloblastoma (MB) is the most common malignant brain tumor in children. While standard-of-care, which combines surgery, chemotherapy, and radiation therapy, extends the survival of MB patients, survivors experience treatment-associated long-term side effects, including reduced cognitive and physical abilities, impaired hormonal functions, and an increased chance of developing secondary cancers. Moreover, some MB tumors develop resistance to standard-of-care, causing fatal relapse. These outcomes urge for deeper understanding of the cellular and molecular mechanisms that drive MB growth and the development of mechanism-based and safe treatment approaches to benefit MB patients.
Project Goals
In this project, we will elucidate MB disease mechanism by studying the interactions between cerebellum granule neurons, the most numerous neurons in the brain, and tumor cells. Using human MB cell lines and preclinical mouse models, we will reveal how granule neuron-secreted molecules are perceived by tumor cells. Further, we will determine the therapeutic efficacy of repurposing an U.S. FDA approved anti-epilepsy drug to inhibit neuron-cancer interaction for reducing MB growth. We anticipate our findings to provide the first evidence that neurons drive MB growth and establish the proof-of-principle that targeting neuron-cancer interaction using an approved drug is an effective and safe way to treat MB. We envision our preclinical findings to provide the foundation for a future clinical trial.
