Testing mTOR Inhibition in NF1-driven Low Grade Glioma

Background

Pediatric low-grade gliomas represent the most common group of brain tumors in children. Traditional therapies, such as irradiation and conventional chemotherapy, can prevent clinical progression, but many tumors regrow, requiring additional therapy. Also, there are many harsh side effect to the treatment. Therefore, new therapeutic strategies are needed. Type 1 neurofibromatosis (NF-1) is the most common genetic disorder across the globe. Approximately 20% of children with a NF-1 gene mutation develop a low-grade glioma brain tumor. Loss of the NF-1 gene leads to increased cell growth and activation and a growth pathway called mTOR.

Project Goal

Laurence will be working to determine the efficacy of a drug inhibiting mTOR in cells lacking NF-1. They will measure proliferation, growth, and cell death after inhibitor treatment, as well as place the cells into immunodeficient mice to see if they will form brain tumors. These experiments will provide the preclinical justification for advancing new mTOR inhibitors into clinical trials for pediatric brain tumors with NF-1 mutations.