Integrating Molecular Pathology, Tumor Microenvironment, and Novel Therapies to Overcome Resistance in Glioblastoma

Area of Science:

• Neuro-oncology
• Cancer Biology
• Genomics

Background:

• Glioblastoma multiforme (GBM) is the most aggressive adult primary brain tumor, marked by heterogeneity, rapid progression, and treatment resistance.
• Recurrence is driven by glioma stem-like cells (GSCs), adaptive signaling, and an immunosuppressive tumor microenvironment (TME).
• Molecular profiling reveals alterations (e.g., EGFR amplification, IDH mutations), but integrating multi-omics data for therapy development remains challenging.

Purpose of the Study:

• To review current limitations in glioblastoma multiforme (GBM) treatment.
• To examine recent advances in molecular classification, signaling pathways, metabolic reprogramming, and non-coding RNA regulation in GBM.
• To highlight novel therapeutic strategies and the role of AI in GBM management.

Main Methods:

• Comprehensive literature review integrating molecular classification, signaling pathways, metabolic reprogramming, and non-coding RNA regulation.
• Analysis of novel therapeutic strategies including nanomedicine, oncolytic virotherapy, immunotherapy, tumor-treating fields, and phytochemicals.
• Exploration of artificial intelligence (AI) and machine learning (ML) applications in GBM diagnosis and personalized treatment.

Main Results:

• Identified limitations in current GBM therapies due to tumor heterogeneity, GSCs, TME, and challenges in multi-omics data integration.
• Detailed recent developments in understanding GBM molecular landscape and regulatory mechanisms.
• Highlighted promising novel therapeutic avenues and the potential of AI/ML for precision medicine.

Conclusions:

• Effective GBM treatment requires addressing blood-brain barrier penetration, therapeutic resistance, and immune evasion.
• Integrating mechanistic and translational insights is crucial for advancing precision medicine in GBM.
• Novel strategies and AI hold significant promise for improving patient outcomes in glioblastoma multiforme.