Subependymal giant cell astrocytoma: Role of mTOR pathway and its inhibitors

Abstract

Subependymal giant cell astrocytoma is a distinct brain tumor growing near the foramen of Monro. Although histologically benign, these tumors may produce hydrocephalus and are associated with significant morbidity and mortality. Until recently, the only recommended treatment for these tumors was surgical resection. Subependymal giant cell astrocytoma is almost exclusively associated with Tuberous Sclerosis Complex. Tuberous Sclerosis Complex is a relatively frequent neurocutaneous disease, caused by the mutation in either of two genes: TSC1 or TSC2. Both genes act as tumor suppressors, and their products were shown to inhibit mTOR pathway. Recently, the recognition of the role of mTOR pathway in the pathogenesis of Tuberous Sclerosis Complex and subependymal giant cell astrocytoma led to clinical trials of mTOR inhibitors. Everolimus was shown to reduce the size of subependymal giant cell astrocytoma and is currently approved by FDA to treat patients with SEGA associated with TSC, who cannot be treated with surgery.