Glioblastoma

P1, N=10, Active, not recruiting, University of Chicago | Completed --> Active, not recruiting | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Jun 2025

The regimen was ineffective in bevacizumab-naïve patients and only narrowly met its predetermined endpoint in patients with prior BEV. These results do not support the combination regimen as tested in this protocol for further investigation in GBM.

Functionally, endothelins reduced proliferation while promoting migration and PMT via EDNRB-dependent Ca2+ signaling, ERK/STAT3 activation, and apamin-sensitive SK2/SK3 potassium channel activity. Collectively these findings establish endothelin signaling as an important regulator of glioma cell plasticity and behavior.

We also proposed a novel adverse outcome pathway (AOP) framework linking PFOA/PFOS exposure to GBM, offering critical toxicological insights. Overall, these findings provide valuable evidence for the potential toxicological impact of PFOA/PFOS on GBM, highlighting the necessity for further mechanistic investigations.

These results indicate that [111In]In-DTPA-EphA2-57-1 is a promising SPECT probe for the noninvasive assessment of EphA2 expression. Additionally, the findings may inform future EphA2-targeted theranostic applications.

GBM cell lines exhibited elevated MUC1 mRNA and protein levels vs. NHA (p < 0.001). MUC1 correlation with glioma malignancy and patient outcomes represents a prognostic biomarker and potential therapeutic target, underscoring its relevance in neuropathology practice.

CYT-6091, a ~27 nm PEGylated gold nanoparticle conjugated with TNF-α, enabled systemic delivery of this cytokine without inducing severe hypotension, showing a substantially improved safety profile compared with free TNF-α...Collectively, these findings highlight the capacity of MNPs to integrate diagnostic and therapeutic functions, including MRI/CT contrast enhancement, magnetic hyperthermia, photothermal and photodynamic therapies, and gene delivery. Despite significant progress, challenges related to heterogeneous biodistribution, long-term toxicity, and regulatory approval remain, emphasizing the need for the development of safer and more efficient metallic nanomedicines aligned with emerging clinical demands in personalized medicine.

Despite promising anti-tumor activity in vitro, the clinical efficacy of PRMT5 inhibitors is often limited by the tumor microenvironment, particularly the impact of non-malignant cells that attenuate drug activity. Finally, we explore rational combination strategies that integrate PRMT5 inhibition with existing therapies to enhance clinical outcomes in GBM.

First, the efficacy of various drugs, including paclitaxel (PTX), doxorubicin (DOX), temozolomide (TMZ) and Gboxin is tested in GBM, endothelial and monocytic cell lines in order to evaluate the ideal drug to be loaded in our monocyte-nanoparticle delivery system. Importantly, conjugation of NPs to BMDMs with 1:5000 cell:NP ratio does not affect the transmigration ability of the monocytes and NPs show improved brain targeting when are conjugated to BMDMs compared to free injected NPs, in an orthotopic GBM mouse model. Overall, our data provides evidence for successful targeting of GBM tumors in mice with our BMDM-PLGA-PTX delivery system, holding promise as a future therapeutic strategy.

P=N/A, N=57, Terminated, Pediatric Brain Tumor Consortium | N=300 --> 57 | Trial completion date: Jul 2028 --> Apr 2026 | Suspended --> Terminated | Trial primary completion date: Jul 2027 --> Apr 2026; The NCI will not extend the PBTC grant beyond March 31, 2026.

Importantly, small-molecule screening identified T7117 as an inhibitor that disrupts the TRIM25-HIF-1α interaction, suppresses tumor growth, and enhances temozolomide efficacy. Together, our findings uncover a previously unrecognized ubiquitin mechanism that stabilizes hydroxylated HIF-1α under normoxia, revealing the TRIM25-HIF-1α axis as a driver of GBM pseudohypoxia and a potential therapeutic target.