GAST and central nervous system cancer: While many different oHSV-1 vectors have been proposed in the context of glioblastoma treatment, essentially three main types of oHSV-1 have been used: (1) vectors with deletions in the γ34.5 neurovirulence factor gene, which proved to be very safe in both animal and clinical studies but showed excessive attenuation in glioma stem cells [41]; (2) vectors with an additional deletion of the ribonucleotide reductase major subunit (ICP6) gene, to completely restrict viral replication to cells with active DNA replication.