Background
tumor, death
GLIOBLASTOMA MULTIFORME (GBM), TUMOR, RECURRENCE, MALIGNANT BRAIN TUMOR
Despite various improvements, the treatment of glioblastoma multiforme (GBM) as the most common primary malignant brain tumor in adults remains a challenge. Given the highly aggressive nature of the GBM, current therapy, including radical resection, radiation, and chemotherapy, could improve the patient survival merely to a limited extent, and almost all patients show recurrence with a 5-year survival rate of 6.8% [Gene therapy has gained popularity as a potential therapeutic modality for GBM during recent decades. In this regard, various approaches have been investigated in prior preclinical studies, including suicide gene therapy, immunomodulatory gene therapy, tumor-suppressor gene therapy, and oncolytic viral therapy [Suicide gene therapy using the engineered ADSCs mainly consists of delivering the HSV-TK to the tumor microenvironment and administration of a prodrug, such as ganciclovir. Following the use of ganciclovir, the HSV-TK phosphorylates it and produces a cytotoxic metabolite, which in turn could inhibit the DNA polymerase and result in cell death. After the production of phosphorylated toxic metabolites, they could be transferred from the ADSCs expressing the HSV-TK to the tumor cells and exert a cytotoxic impact on them through various potential pathways, such as gap junctions, apoptotic vesicles, paracrine immunostimulation, and autophagy inhibition [Clinical evidence concerning the use of stem cells in gene therapy for GBM is significantly limited. Our previous study has been the only one thus far to evaluate the safety and feasibility of suicide gene therapy using autologous bone marrow-derived MSCs (BMSCs) carrying the HSV-TK gene in patients with newly diagnosed GBM [