Glioblastoma

P2, N=75, Recruiting, Institut de cancérologie Strasbourg Europe | Not yet recruiting --> Recruiting | Trial completion date: Mar 2027 --> Jul 2029 | Trial primary completion date: Mar 2027 --> Jul 2028

P1, N=12, Recruiting, University of Pennsylvania | Not yet recruiting --> Recruiting

Indeed, orthotopic implantation of MET-expressing GBM cells corroborates their superior tumor-initiating and invasive capabilities. Thus, pericytes represent critical modulators of GBM development by orchestrating a tumor-suppressive microenvironment, highlighting the importance of their preservation in therapy.

Glioblastoma mounts a spatial self-protective defense through IL-8-driven TSR formation that restricts oncolytic virus spread. IL-8 functions as both a pharmacodynamic biomarker and a therapeutic target, and its inhibition provides a rational strategy to overcome resistance and optimize GBM virotherapy.

Moreover, GBM tissue samples showed LARG S1288 phosphorylation and RhoA-GTP-bound RhoA. Elucidating the regulatory mechanisms governing this process is crucial for the development of LARG-targeted therapeutic interventions.

FACS analysis showed loss of co-stimulatory CD80, an immune synapse component, following B3gat1 knockdown. These results suggest that loss of HNK-1 expression contributes to tumor immune escape through loss of immune recognition and attack via downregulation of tumor cell surface co-stimulatory molecules, leading to reduced CD8+ T-cell activation and immune synapse formation, and increased T-cell apoptosis.

Despite its efficacy, G3-CYS displayed a narrow therapeutic window with pronounced cytotoxicity above 1 μM. In vivo studies further confirmed dose-dependent systemic toxicity, likely associated with enhanced blood coagulation.

Western blot analysis confirmed that HDAC inhibition increased AcH3K9 protein levels. Further, studies in in vivo xenograft model and allograft C6 Wistar rat model revealed strong antitumour activity, suggesting that compound 3B is a promising therapeutic candidate for glioblastoma treatment.

This led to the in silico identification of a novel lead compound with a distinct thiazolopyridine-based scaffold and high predicted potency. Our findings demonstrate how integrated bioinformatic pipelines can dissect the complex landscape of GBM resistance, contextualize the roles of key oncogenes, and guide the rational design of potential new inhibitors.

The Se(B-CD-CA-4-NPs) complex represents a promising multifunctional therapeutic agent for GBM, offering enhanced proapoptotic property, selective tumor targeting, and reduced toxicity.

We found that β-lapachone acts synergistically with TMZ to inhibit GBM cell proliferation, epithelial-mesenchymal transition (EMT), and angiogenesis by suppressing NF-κB activation through blockade of p65 nuclear translocation. These results provide a solid preclinical foundation for combining β-lapachone with TMZ as a promising strategy to counteract TMZ resistance in GBM.

A general drug resistance to TRK-inhibition was documented. This study addresses the complex and adaptive nature of pediatric epithelioid glioblastomas and highlights the need for continued molecular profiling from relapses and various tumor regions to enable multitarget treatment approaches.