Human Cytomegalovirus as a Therapeutic Target in Glioma Stem Cells

Glioblastoma is the most aggressive tumor among gliomas, and recurrence remains inevitable despite aggressive therapies. Resistance to existing treatment modalities is attributed in part to the presence of glioma stem cells, which comprise a distinct cell subpopulation that sustains cell renewal and tumor evasion through multiple mechanisms. Therapeutic strategies using herpesviruses have been evaluated following the discovery of differential human cytomegalovirus (HCMV) expression in glioblastoma tumor cells. The absence of expression in normal brain tissue led to multiple clinical trials demonstrating the potential clinical utility of targeted HCMV via herpesvirus-based oncolytic therapeutic strategies. This review provides a comprehensive overview of existing studies evaluating the expression and biological significance of HCMV within glioma stem cells. Targeting HCMV in this cellular compartment may disrupt the continuous cellular support and resilience of glioblastoma stem cells, thereby enhancing the efficacy of current treatments.