Tuning epigenetics to enhance cancer virotherapy

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immune responses. Recent advances highlight the strong synergistic potential of combining epigenetic inhibitors with oncolytic viruses. This strategy enhances viral replication and tumor cell killing, reprograms the tumor microenvironment, and ultimately improves therapeutic efficacy. Consequently, the integration of epigenetic modulators with OV therapy represents a promising frontier in oncology. This review comprehensively examines epigenetic inhibitors, with emphasis on their combined application with oncolytic viruses for cancer treatment.