Glioblastoma Research [Neurosurgery Wiki]

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====== Glioblastoma Research ======

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===== Key areas of ongoing glioblastoma research =====


==== 1. Molecular and Genetic Insights ====

- **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.


==== Innovative Therapeutic Approaches ====

#### **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.

---

### **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 =====

[[Artificial Intelligence for glioblastoma research]]