Biology and clinical management challenges in meningioma.

Meningiomas are the most frequently occurring intracranial tumors. They are characterized by a broad spectrum of histopathologic appearance. Molecular alterations driving meningioma development, which affect the NF2 gene, are found in roughly 50% of patients. Rare genetic events in benign meningiomas are mutations in TRAF7, KLF4, AKT1, and SMO; all of these mutations are exclusive of NF2 alterations. Progression to a clinically aggressive meningioma is linked to inactivation of CDKN2A/B genes, and a plethora of signaling molecules have been described as activated in meningiomas, which supports the concept of successful clinical use of specific inhibitors. Established treatments include surgical resection with or without radiotherapy delivered in a single fraction, a few large fractions (radiosurgery), or multiple fractions (fractionated radiotherapy). For recurrent and aggressive tumors, inhibitors of the vascular endothelial growth factor (VEGF) pathway, such as vatalinib, bevacizumab, and sunitinib, showed signs of activity in small, uncontrolled studies, and prospective clinical studies will test the efficacy of the tetrahydroisoquinoline trabectedin and of SMO and AKT1 inhibitors.