Next-Generation Therapies for Meningioma: Overcoming Barriers and Expanding Treatment Options

Meningioma is the most common primary brain tumor. Surgical resection and, in some cases, adjuvant radiotherapy remain the cornerstone of treatment, offering an exceptionally high cure rate. However, treatment can be challenging, particularly in cases of high-grade tumors, symptomatic tumors located in eloquent brain regions, and in patients who are medically inoperable. Recent molecular profiling has redefined meningioma classification, identifying distinct consensus groups-Immunogenic (MG1), NF2-wildtype (MG2), Hypermetabolic (MG3), and Proliferative (MG4)-with significant prognostic and therapeutic implications. This review discusses the latest advancements in precision medicine therapeutic approaches in meningioma, with a focus on overcoming existing barriers and expanding treatment options. We explore how molecular insights may guide novel therapeutic strategies, including targeted agents against the PI3K/AKT/mTOR and Sonic Hedgehog pathways (e.g., everolimus, vismodegib), CDK4/6 inhibitors (e.g., palbociclib, abemaciclib), angiogenesis inhibitors (e.g., sunitinib), and immunotherapies such as PD-1/PD-L1 checkpoint inhibitors. Additionally, we examine innovative modalities like peptide receptor radionuclide therapy (PRRT) and advanced radiation techniques. A key area of exploration is the challenge posed by treatment resistance and inter-patient variability, underscoring the crucial need for biomarker-driven, personalized treatment strategies to optimize clinical outcomes for meningioma patients.