Molecular advances in high-grade glioma: From diagnosis to the hope of precision therapy
High-grade gliomas, particularly glioblastoma, remain among the deadliest primary brain tumors, with a median survival under 18 months despite aggressive multimodal therapy. The 2021 World Health Organization classification integrated molecular markers with histology, transforming diagnostic and therapeutic paradigms. IDH mutation status, MGMT methylation, and comprehensive genomic profiling now guide treatment decisions and provide critical prognostic information. Despite targeted therapy successes in other cancers, glioblastoma’s profound intratumoral heterogeneity, redundant signaling pathways, impenetrable blood–brain barrier, and immunosuppressive microenvironment have limited single-agent efficacy. However, recent immunotherapy breakthroughs, particularly chimeric antigen receptor (CAR)-T cells with dramatic early responses, combined with novel delivery systems and rational combinations, offer renewed hope. This review synthesizes current molecular diagnostics, targeted therapies, emerging immunotherapeutic approaches, and technological innovations, emphasizing that future progress requires precision medicine integrating comprehensive profiling with multimodal treatments tailored to individual tumor biology.
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