Glioblastoma

P=N/A, N=176, Recruiting, University Hospital, Essen | Not yet recruiting --> Recruiting

P2, N=38, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P=N/A, N=20, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

In conclusion, SIX5 functions as a critical oncogenic driver in GBM, regulated by KDM5C and promoting tumor progression through UBE2C-mediated activation of AKT/mTOR signaling and glycolytic reprogramming. The KDM5C-SIX5-UBE2C regulatory axis represents a potential prognostic biomarker and therapeutic target in glioblastoma.

These combined actions lead to cell cycle arrest and mitotic catastrophe. Our findings establish Z5 as a promising clinical candidate for classical GBM, employing a unique dual mechanism that overcomes EGFR-targeted and DNA-damaging therapy limitations by synergistically targeting DNA and EGFR with high efficacy, advancing understanding of EGFR-WEE1 biology, and supporting clinical development.

Mechanistically, ARHGEF26 interacted with and stabilized the core stemness transcription factor SOX2 by reducing its K48-linked poly-ubiquitination and subsequent proteasomal degradation. Our findings reveal a novel role and mechanism for ARHGEF26 in promoting GBM stemness and suggest its potential as a therapeutic target.

In agreement, molecular docking analyses identified sterol-binding pockets. The data on both cholesterol and oxysterols suggests that ASC1 regulation may rely on a structurally specific sterol-protein interaction rather than general alterations of membrane biophysics, with potential relevance for conditions characterized by altered membrane cholesterol composition in cholesterol-rich tissues.

Network pharmacology analysis revealed that beyond HMGCR, mevastatin may directly interact with 12 additional targets relevant to GBM treatment. MD simulations elucidated its binding mechanisms to MAPK1, MDM2, MMP2, and GRB2. In summary, starting from a series of multi-target and multifunctional natural product derivatives sharing the same core scaffold, this study identified a small molecule that exhibits higher efficacy, lower toxicity, and potential multifunctional activity compared to the reference compound, thus proposing a novel strategy for the discovery of multi-target, multifunctional therapeutic agents.

Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation...Temozolomide in combination with siRNA-mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.

These nanobody-displaying AAV greatly enhanced the transduction of CD73- or P2X7-expressing HEK cells in vitro and patient-derived glioblastoma cells ex vivo. Our results pave the way for the therapeutic application of these nanobody-displaying AAV, for example, to express immune-activating cytokines or checkpoint inhibitors in the tumor cells to turn a cold tumor microenvironment hot.

In vitro experiments confirmed the cytotoxicity and induction of methuosis in GBM cells by AP@CM-Ang, accompanied by the release of immune-stimulatory factors. In vivo experiments demonstrated that the nanodrug significantly enhanced tumor targeting, effectively inhibited tumor growth, and increased immune cell activation, validating its potential as a promising and safe strategy for GBM treatment.