Clinical and Translational Advances in Primary Brain Tumor Therapy with a Focus on Glioblastoma-A Comprehensive Review of the Literature

This comprehensive review paper examines the most updated state of research on glioblastoma, an aggressive brain tumor with limited treatment options. By analyzing 76 recent studies, from translational and basic sciences, to clinical trials, we highlight various aspects of glioblastoma and shed light on potential therapeutic strategies. The interplay between tumor cells, neural progenitor cells, and the tumor microenvironment is explored. Targeting the PI3K-Akt-mTOR pathway through extracellular-vesicle (EV)-mediated signaling emerges as a potential therapeutic strategy. Personalized modeling approaches utilizing patient-specific MRI data offer promise for optimizing treatment strategies. The response of glioblastoma stem cells (GSCs) to different treatment modalities is examined, emphasizing the need to inhibit the transformation of proneural (PN) GSCs into resistant mesenchymal (MES) GSCs. Metabolic therapy and combination therapies show potential in reversing treatment resistance and inhibiting both PN and MES GSCs. Immunotherapy, targeted approaches, and molecular dynamics in gliomas are discussed, providing insights into early-stage diagnosis and treatment. Additionally, the potential use of Zika virus as an oncolytic agent is explored. Analysis of phase 0 to 3 clinical trials reveal promising outcomes for various experimental treatments, highlighting the importance of combination therapies, predictive signatures, and patient selection strategies. Specific compounds demonstrate potential therapeutic benefits and tolerability. Phase 3 trials indicate the efficacy of DCVax-L in improving survival rates and depatux-m in prolonging progression-free survival. These findings emphasize the importance of personalized treatment approaches and continued exploration of targeted therapies, immunotherapies, and tumor biology understanding in shaping the future of glioblastoma treatment.