Rethinking Meningioma Biology: Integrating Molecular and Microenvironmental Insights for Mechanism-Guided Therapy.

Abstract

Meningiomas are the most common primary intracranial tumors, accounting for 42.6% of all central nervous system tumors. Although many meningiomas are indolent, clinical behavior is highly heterogeneous, with recurrence occurring in a minority of low-risk tumors but in more than half of clinically high-risk cases despite standard therapy. During the past decade, significant advancements in molecular profiling have provided insights into meningioma biology and have begun to influence clinical practice. Genomic sequencing, DNA methylation profiling, and gene expression analyses have revealed distinct molecular subgroups with prognostic and therapeutic implications. These advancements, coupled with a growing understanding of the meningioma immune microenvironment, have expanded therapeutic possibilities beyond traditional surgery and radiation approaches. Here, we review how molecular profiling is refining patient stratification and treatment selection, examine the evidence supporting various therapeutic approaches, and explore ongoing clinical trials. Finally, we highlight the critical challenges in advancing personalized medicine for meningioma patients. This comprehensive review provides an integrated overview of current diagnostic and treatment paradigms while offering perspectives on future directions in meningioma therapy.