Principal Investigator: Mark Kieran, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts

Low-grade gliomas are the most common brain tumor in children. While a portion of patients are effectively cured with surgery alone, for a significant majority, especially those without neurofibromatosis type 1, recurrences are common. These patients often require repeated resections, chemotherapy and radiation therapy.

The damage caused by these therapies has a significant impact in the lives of these children. More targeted and less toxic therapies in this population are therefore required. An important pathway that has been implicated in pediatric low-grade gliomas is mTOR, a central relay site within the cell that when activated, results in increased proliferation, cell migration and angiogenesis.

Our preliminary work has demonstrated the presence and activation of this pathway in LGGs samples from children without NF1. RAD001 is a new oral mTOR inhibitor that has demonstrated excellent inhibition of this pathway at clinically achievable doses. The drug is exceedingly well tolerated and is currently used to reduce the risk of solid organ transplant rejection. We are now proposing a formal multi-institutional clinical trial of RAD001 in non-NF1 children with recurrent or progressive LGGs after standard treatment.