INTRODUCTION: Better understanding of aberrantly active molecular pathways in 
tumors offers potential to develop more specific and less toxic therapies. 
Abnormal mammalian target of rapamycin (mTOR) complex signaling and defects in 
TSC1 and TSC2 have been associated with the development of subependymal giant 
cell astrocytomas (SEGAs) in tuberous sclerosis complex (TSC) patients. 
Recently, mTOR inhibitors such as everolimus have shown encouraging benefit for 
patients with SEGAs.
AREAS COVERED: The authors discuss a molecular genetic pathway linked with TSC, 
specifically the role of two proteins whose functional absence is responsible 
for most SEGA tumors that arise in TSC patients. The authors also examine the 
rationale for targeted agents against this pathway therapeutically and describe 
the clinical evidence underlying the FDA approval of everolimus for patients 
with inoperable SEGAs.
EXPERT OPINION: Everolimus (Afinitor) selectively targets a molecular defect of 
SEGAs in TSC patients. Although surgery is effective, most SEGAs recur. An agent 
that inhibits an underlying molecular abnormality represents a particularly 
attractive therapeutic option for patients with inoperable or recurrent tumors. 
Studies are also underway to assess everolimus in treating other sequelae of 
TSC, and other gliomas. Finally, additional research aimed at better 
understanding aberrant cell signaling pathways may lead to the development of 
more effective therapeutics.