Glioblastoma

In three-dimensional (3D) spheroids, compound 45 reduced the cumulative spheroid area approximately 10-fold more than the single-target inhibitors FK866 or SLC-0111 and induced apoptosis through NAD depletion, mitochondrial dysfunction, and suppression of ERK/mTOR signaling. These results support dual hCA IX/XII-NAMPT inhibition as an effective strategy to impair tumor growth and survival under hypoxic stress.

This unexpected finding prompted contrast-enhanced MRI brain, which identified a peripherally enhancing splenium lesion concerning for neoplasm. Stereotactic biopsy confirmed GFAP-positive, diffuse high-grade glioblastoma, IDH-wildtype, WHO Grade 4, highlighting the role of FDOPA PET in the assessment of primary brain tumors.

Overall, our results elucidated that TEAD4-driven GPX8 suppresses mitochondrial oxidative stress in TMZ-resistant cells through activation of the CTHRC1/p38 MAPK/FOXO3 pathway, which promotes TMZ resistance in GBM cells. These findings suggest that GPX8 may serve as a novel therapeutic target for overcoming TMZ resistance in GBM.

We unveil MSN as a non-canonical GRK5/HDAC7 axis that promotes glioma malignancy by modulating the cortactin/MSN/CD44 pathway. Targeting this axis potentially represents a promising therapeutic strategy against gliomas.

SRY-box transcription factor 9 was highly expressed in GBM and this activated CLCF1 expression as one of its transcription factors to further enhance GBM development. Thus, CLCF1 regulated by SOX9 can enhance the development and immune evasion of GBM.

Lead compound 9e (K d = 19.11 μM) reduced viability and STAT3 signaling in 3D GBM spheroids. These findings demonstrate the potential of reactivity-aware ultralarge screening to identify modulators of nonenzymatic, dynamic targets in complex cancer models.

Intriguingly, within GBM tissues, we further confirmed the expression of SERPINA3 in GAMs, and that SERPINA3 expression is positively associated with CD68 and IBA1 in primary gliomas, indicating remodeling of the tumor immune microenvironment. This study provides an insight into the therapeutic strategy targeting SERPINA3 in glioma patients.

β-BA exerts potent anti-GBM activity by inducing mitochondrial dysfunction and NLRP3-mediated pyroptosis, providing a mechanistic basis for developing β-BA as a promising natural therapeutic candidate for GBM. The online version contains supplementary material available at 10.1007/s13205-025-04691-x.

This review did not identify definitive clinical or histomolecular differences between pediatric and adult HGAP, underscoring the need for further comparative studies. Pediatric HGAP may represent an underrecognized diagnostic entity within the glioma spectrum, emphasizing the critical role of methylation profiling for accurate diagnosis and classification. Retrospective reclassification of histologically and molecularly ambiguous gliomas is warranted and may reveal additional cases. Larger pediatric cohorts are urgently needed to inform clinical management and refine prognostic stratification.

The present analysis of prognostic outcome associations of PA-PPI use in patients with recurrent glioblastoma provides no evidence that PA-PPI use may compromise outcome in this setting. The disconnect between clear outcome associations in the first-line setting, without a link to MGMT promoter methylation, versus no associations in the recurrent setting may be linked to changing prescriptions patterns, but requires further studies. Since alternative medications are available, the indications for PA-PPI prescription should probably be narrowed in patients with glioblastoma.

These findings suggest that NRP1 may regulate radiosensitivity by modulating DNA repair pathways in p53-mutated GBM T98G cells. NRP1 could serve as a potential therapeutic target for improving the response of radioresistant tumors such as GBM.

We describe that proton therapy resulted in less lymphopenia than proton radiation, and propose that the mechanism may be related to biological processes rather than solely decreased exposure of circulating lymphocytes. This may be used to guide incorporation of immune therapy in GB.