Glioma

P1/2, N=10, Active, not recruiting, InSightec | Recruiting --> Active, not recruiting | Trial completion date: Jul 2026 --> Oct 2026 | Trial primary completion date: Jan 2026 --> Jun 2026

P1, N=20, Recruiting, Washington University School of Medicine | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

P1, N=94, Recruiting, Mayo Clinic | Trial completion date: Feb 2029 --> May 2029 | Trial primary completion date: Feb 2028 --> May 2028

In orthotopic syngeneic GBM models, Mn-CDs remodel the immunosuppressive tumor microenvironment, suppress intracranial tumor progression, and prolong survival with favorable biosafety. Collectively, this work establishes a dual-targeted Mn-based carbon nanoplatform that converts GBM toward an immune-responsive state through convergent cGAS-STING activation and ICD-driven immune priming.

To enable clinical translation, we developed SRN-101, a clinical-grade AAV-hIFNβ construct with optimized potency and manufacturability, which achieved superior expression and in vivo efficacy vs. the research-grade vector. These findings establish AAV-vectorized cytokines as a durable, locally delivered immuno-gene therapy platform for high-grade gliomas.

A central thesis of this review is that these six contextual determinants establish a framework for understanding receptor pleiotropy. Furthermore, while targeting Plexin-B signaling shows therapeutic promise (eg, pepinemab in clinical trials), indiscriminate inhibition risks abrogating tumor-suppressive functions and perturbing immune microenvironment homeostasis, underscoring the necessity for biomarker-driven stratification to prevent paradoxical oncogenic consequences.

These findings collectively suggest that upregulation of IKBIP promotes the proliferation and invasive behaviors of glioma cells by activating the Wnt/β-catenin/EMT pathway. Overall, our findings suggest that SP1-IKBIP axis facilitates the proliferation and invasion of glioma through Wnt/β-catenin-associated EMT, and SP1-IKBIP axis may represent a promising target for the clinical diagnosis and treatment of glioma.

Our data suggest that polycystins, PC1 in particular, exert conserved yet context-dependent mechanoregulatory functions in solid tumors. By influencing EMT, migration, tumor progression, and TAZ-mediated mechanotransduction, PC1 emerges as a potential biomarker and mechanotherapeutic target in mechanically responsive cancers.

Moreover, the GBM tumor microenvironment (TME) is enriched in arachidonic acid (AA)-derived cyclooxygenase (COX) products prostaglandins (PG) E2 and F2α in combination with enhanced CD24 expression. By our comparative approach, the data hint toward a pro-tumorigenic Siglec10+CX3CR1+ macrophage population depending on the characteristic tumor microenvironment (TME) of highly malignant GBMs.

Knocking down ALG1 significantly reduced glioma cell migration and downregulated EMT-related proteins like N-cadherin, β-catenin, and Vimentin. This study highlights ALG1 as a key prognostic biomarker and therapeutic target for glioma, promoting malignancy through increased cell migration, EMT modulation, and an altered immunosuppressive microenvironment.

This transporter protein demonstrated significant enrichment in pathways characteristic of the tumor stromal niche. These results establish MFSD2A as an immunological determinant in LGG pathogenesis, providing mechanistic insights into its prognostic and therapeutic relevance.

P1/2, N=26, Recruiting, Memorial Sloan Kettering Cancer Center