Emerging Meningioma Therapies I: Precision Medicine, Targeted Therapies, and Mutation-Specific Approaches

Traditional chemotherapies and hormonal agents have been associated with disappointing results in the treatment of progressive/recurrent meningioma, and there are no FDA-approved systemic treatments for this indication. The development of effective systemic therapies remains an area of active investigation in the field. Recently, advances in tools for molecular characterization of cancer have improved our understanding of the underlying molecular landscape of meningiomas and their progression to more aggressive phenotypes. Large-scale genetic analyses have revealed that mutations in the NF2 gene are found in 50–60% of meningiomas (both inherited and sporadic) and that mutations in other genes such as TRAF7, SMO, AKT1, and KLF4 are often found in tumors without NF2 mutations. Clinical trials using targeted therapies aimed at disrupting the signaling pathways affected by these mutations are underway. Furthermore, genetic and epigenetic information, including the above mutations, methylation status, and mutational load, have all been identified as potential biomarkers to predict prognosis and recurrence and may provide new avenues for therapeutic intervention. In this chapter, we describe emerging systemic therapies and treatment strategies based on the current understanding of the genetic and molecular changes underlying meningioma tumorigenesis.