Advancing Gene Therapy for Glioblastoma: Cutting-Edge Strategies and Precision Delivery in Neurosurgical Oncology

Abstract Glioblastoma multiforme (GBM) is a highly aggressive and treatment-resistant brain tumor with poor prognosis, characterized by rapid growth, genetic heterogeneity, and invasiveness. Despite the use of maximal surgical resection, radiotherapy, and chemotherapy, the median survival for GBM patients remains limited to 12-15 months. Gene therapy has emerged as a promising avenue for addressing the molecular complexities of GBM, offering precise, personalized approaches to tumor treatment. This review explores the latest advancements in gene therapy for GBM, focusing on cutting-edge strategies such as CRISPR-Cas9, viral vector-based delivery systems, and suicide gene therapy. Viral vectors like adenoviruses and adeno-associated viruses (AAVs) have been used to deliver therapeutic genes directly to tumor cells, while CRISPR-Cas9 has shown promise in targeting oncogenes such as EGFR and correcting tumor suppressor mutations. Challenges related to the blood-brain barrier (BBB), tumor heterogeneity, and gene therapy delivery are also discussed, along with emerging solutions like nanoparticle delivery systems and oncolytic viruses. As gene-editing technologies evolve, the integration of these therapies with conventional treatments offers new hope for improving survival and quality of life in GBM patients. This review highlights the transformative potential of gene therapy in neurosurgical oncology and underscores the need for continued research to overcome existing obstacles and optimize precision delivery in the treatment of GBM.