Pharmacologic management of tuberous sclerosis complex-associated subependymal giant cell astrocytomas

Abstract

Introduction: Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the development of noncancerous tumors throughout the body. Lesions affecting the brain include subependymal nodules, tubers and subependymal giant cell astrocytomas (SEGAs). SEGAs, in particular, can result in significant morbidity and mortality if they grow large enough to cause obstruction of cerebrospinal fluid flow. Most TSC patients have mutations in either the TSC1 or the TSC2 gene, which result in constitutive upregulation of the mammalian target of rapamycin (mTOR) pathway. Elucidation of the molecular mechanisms responsible for causing TSC led to approval of the first pharmacologic treatment, everolimus, an oral mTOR inhibitor.Areas covered: This review provides an overview of TSC and major manifestations of the disease, specifically SEGA. Everolimus, the first FDA-approved mTOR inhibitor for treating TSC, and sirolimus are described in detail; safety and efficacy data are provided as scientific evidence of their clinical utility in TSC. Special sections on treating young patients and managing adverse events (AEs) are included, as these are two areas of interest among clinicians, because TSC manifestations may be present as early as in utero, and mTOR inhibitors are used in long-term therapy.Expert opinion: One of the many benefits of mTOR inhibitors is their ability to target the underlying pathology of TSC disease. Continued efforts and accrual of clinical data will further refine and optimize the treatment and management of TSC patients.