Reassessing Viral Gene Therapy for Glioblastoma: Translational Opportunities and Challenges.

Glioblastoma is a highly invasive primary brain tumor with a remarkably poor prognosis. Resistance to the current gold standard treatment, maximal safe surgical resection followed by radiation and chemotherapy, has led to an investigation into novel therapeutic alternatives, notably gene therapy. This perspective evaluates the translational potential of three prominent viral gene therapies for glioblastoma, highlighting the preclinical challenges facing CRISPR-Cas9-mediated gene editing, suicide gene therapy, and oncolytic virus therapy. We assert that clinical translation depends strongly on the optimization of these approaches to overcome biological and delivery barriers. Prioritizing such research is critical, as gene therapies continue to show promise as a much-needed advancement in the field of neuro-oncology.