Year: 2026
Type: review
Study design: Systematic Review
Abstract: The present study critically summarizes recent progress in therapeutic strategies and molecular mechanisms of glioblastoma (GBM) from 2020 to 2025, appraise the strength of evidence underlying emerging treatments, and provide practical references for individualized clinical decision-making. Relevant studies were retrieved from PubMed, Embase and Web of Science using predefined search strings combining 'glioblastoma', 'molecular classification', 'targeted therapy', 'immunotherapy' and 'drug resistance'. After duplicate removal and independent two-reviewer screening, 86 studies were included and synthesized, and the evidence was graded according to study design (randomized trials vs. single-arm early-phase trials vs. preclinical studies). The results demonstrated that molecular classification centered on IDH mutation and MGMT promoter methylation has become the basis of GBM treatment decision-making, although the WHO CNS5 classification now integrates additional diagnostic and prognostic biomarkers (for example, CDKN2A/B homozygous deletion, EGFR amplification, TERT promoter mutation, chromosome 7 gain/10 loss). 5-aminolevulinic acid fluorescence-guided surgery improves the extent of resection, and tumor treating fields provide an additional survival benefit in newly diagnosed GBM. Emerging approaches, including dual-target CAR-T cells, mRNA vaccines and metabolic inhibitors, have shown preliminary signals of activity in recurrent GBM, but most remain investigational and are supported by early-phase trials with small sample sizes. GBM treatment resistance arises from interconnected DNA repair, epigenetic, metabolic, tumor microenvironment and glioblastoma stem cell networks. In conclusion, GBM management is transitioning from empirical therapy toward molecularly guided precision therapy, but the translational gap between promising preclinical findings and proven clinical benefit remains substantial. Multimodal strategies integrating refined molecular classification, blood-brain barrier-penetrant drug delivery and rationally combined, rigorously tested therapies represent the most realistic path to improving GBM outcomes.
Source: Molecular and Clinical Oncology
Institution: Central Hospital of Zibo
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7221609219