AccScience Publishing / BH / Online First / DOI: 10.36922/BH026050006
REVIEW ARTICLE

Molecular advances in high-grade glioma: From diagnosis to the hope of precision therapy

Shounak Ghosh1 Luiza Harutyunyan1 Bertrand Liang1,2*
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1 Department of Neurology, St. Joseph Medical Center, Stockton, California, United States of America
2 Department of Neurology, School of Medicine, University of Colorado Anschutz, Aurora, Colorado, United States of America
Brain & Heart, 026050006 https://doi.org/10.36922/BH026050006
Received: 26 January 2026 | Revised: 31 March 2026 | Accepted: 9 April 2026 | Published online: 5 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

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.

Keywords
Glioblastoma
High-grade glioma
Precision medicine
Biomarker
Targeted therapy
Immunotherapy
Chimeric antigen receptor-T cells
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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