Genetic therapies in Glioblastoma: a review of innovative ap-proaches and their challenges

Glioblastoma (GB) is a highly aggressive brain tumor characterized by high mortality rates and significant resistance to conventional therapeutic approaches such as surgery, chemotherapy, and radiotherapy. This study reviews the main emerging strategies in the field of genetic therapies, with an emphasis on gene editing by CRISPR-Cas9, which enables precise modification of genes related to tumor proliferation and resistance. Anti-angiogenic therapies, aimed at disrupting the formation of new blood vessels sustaining tumor growth, and modulation of glioblastoma stem cells (GSCs), a subpopulation associated with recurrence and therapeutic resistance, are also discussed. Furthermore, the use of oncolytic viruses as therapeutic vectors for selective destruction of tumor cells and stimulation of antitumor immune responses is explored as a promising approach. The analysis highlights significant advancements but also emphasizes considerable limitations, such as efficient therapy delivery, tumor heterogeneity, and potential adverse effects. Integrating these strategies with personalized treatment based on the molecular characteristics of tumors may represent a promising path to overcoming the challenges of GB management. Broader and more rigorous clinical studies are needed to validate the efficacy and safety of these approaches, providing new perspectives to improve the survival and quality of life of patients.