Glioblastoma Research

• Systematic review and epistemic meta-analysis to advance binomial AI-radiomics integration for predicting high-grade glioma progression and enhancing patient management
• Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors
• Targeting the kynurenine pathway in gliomas: Insights into pathogenesis, therapeutic targets, and clinical advances
• Corrigendum: Metabolic-imaging of human glioblastoma live tumors: a new precision-medicine approach to predict tumor treatment response early
• Basic mechanism of mobilizing cell movement during invasion of glioblastoma and target selection of targeted therapy
• Deciphering the dialogue between brain tumors, neurons, and astrocytes
• Design and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors
• Tumor-associated long non-coding RNAs show variable expression across diffuse gliomas and effect on cell growth upon silencing in glioblastoma

- IDH Mutation Status

- MGMT Promoter Methylation: Predicts response to temozolomide (TMZ) chemotherapy.

- TERT Promoter Mutations: Associated with poor prognosis.

- Glioblastoma Subtypes (Proneural, Classical, Mesenchymal): Identified through transcriptomic analysis, influencing treatment strategies.

- Single-Cell RNA Sequencing: Reveals tumor heterogeneity and therapy resistance mechanisms.

#### a. Immunotherapy - Checkpoint Inhibitors: Limited success due to GBM's immunosuppressive microenvironment. - Chimeric Antigen Receptor (CAR) T-Cells: Targeting EGFRvIII, IL13Rα2, and HER2. - Cancer Vaccines: DCVax-L (dendritic cell vaccine) shows promising results in clinical trials. - Oncolytic Viruses: Engineered viruses like DNX-2401 selectively replicate in tumor cells.

#### b. Targeted Therapy - EGFR Inhibitors: Mixed results due to tumor heterogeneity. - PI3K/AKT/mTOR Pathway Inhibitors: Targeting GBM’s frequent PI3K mutations. - BRAF/MEK Inhibitors: Potentially effective in rare GBMs with BRAF V600E mutations.

#### c. Tumor Microenvironment and Blood-Brain Barrier (BBB) Modulation - Repurposing Drugs (e.g., Metformin, Chloroquine): Target metabolic vulnerabilities. - BBB Disruptors (e.g., Focused Ultrasound, Mannitol): Enhance drug delivery. - Anti-VEGF Therapy (Bevacizumab): Used for recurrent GBM but does not improve overall survival.

#### d. Personalized and AI-Driven Approaches - Organoids and 3D Cultures: Patient-derived GBM models for precision medicine. - Artificial Intelligence (AI): Predicts drug response and disease progression. - Liquid Biopsies (cfDNA, miRNAs): Non-invasive monitoring of GBM evolution.

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### 3. Current and Emerging Clinical Trials - Combination Therapies: Investigating TMZ with immune checkpoint inhibitors. - Gene Therapy Approaches: CRISPR and RNA-based therapies targeting GBM mutations. - Tumor-Treating Fields (TTFields, Optune): FDA-approved for GBM, disrupting mitosis using electric fields.

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### 4. Challenges in GBM Research - High Tumor Heterogeneity: Limits effectiveness of single-agent therapies. - Immune Evasion: GBM’s suppressive microenvironment resists immunotherapy. - Drug Delivery Limitations: The BBB restricts many systemic treatments. - Recurrence Mechanisms: Resistance often develops after initial treatment.

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### 5. Future Directions - Neoantigen-Based Personalized Vaccines: Custom therapies based on patient-specific tumor mutations. - Multi-Omics Approaches: Integrating genomics, proteomics, and metabolomics for better therapeutic targeting. - Nanotechnology: Developing nanoparticles for improved drug delivery across the BBB.

Artificial Intelligence for glioblastoma research