MAPK pathway-targeted therapies for pediatric low grade gliomas

The most common pathologic group of childhood brain tumors are low grade gliomas (LGG). LGG comprise a variety of histologies among which pilocytic astrocytoma (WHO grade I) is the most common. Complete resection of LGG portends an excellent prognosis, but this intervention is mainly possible only with hemispheric tumors. For more centrally-located tumors, especially in young children, there is a risk for tumor-related morbidity including visual compromise and endocrinopathies. Given the generally excellent survival outcomes in children with LGG, the goal of interventions is usually to control tumor growth to avoid morbidities. Previously, chemotherapy was the only intervention available for young patients in whom radiation therapy would cause significant neuro-cognitive morbidity. However, with the discovery of the MAPK pathway as the only molecular pathway involved in LGG tumorigenesis, novel classes of drugs known as BRAF and MEK inhibitors have shown great promise and raise the possibility of chronic long-term therapy.