Targeting meningiomas: advances in molecular pathways, drug repurposing, and precision therapy

Meningiomas are the most common primary intracranial tumors in adults, accounting for more than one-third of brain neoplasms. Most are slow-growing, but higher-grade subtypes (WHO grades II–III) often recur, invade surrounding structures, and remain difficult to treat. Surgery, with or without radiotherapy, is still the standard of care, yet outcomes are limited by resistance and the lack of effective systemic therapies. Recent advances in molecular research have revealed diverse mechanisms that drive therapeutic resistance. Genetic and epigenetic alterations such as neurofibromin 2 (NF2) loss and chromatin remodeling defects contribute to radioresistance and treatment failure. The tumor microenvironment supports survival through hypoxia, angiogenesis, immune evasion, and neuronal interactions, while metabolic reprogramming enables adaptation to therapy. These discoveries are guiding new approaches, including targeted inhibitors, immune checkpoint blockade, epigenetic and metabolic therapies, and drug repurposing strategies such as statins, metformin, and mechanistic target of rapamycin (mTOR) inhibitors. At the same time, biomarker development—spanning molecular profiling, liquid biopsy, and functional imaging—is refining risk stratification and patient selection. The management of meningiomas is shifting toward mechanism-based, personalized strategies. Combining molecular insights with targeted therapies, immunomodulation, and repurposed drugs has the potential to overcome resistance and improve outcomes. Continued biomarker development and well-designed clinical trials will be crucial for translating these advances into practice.