Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives

SIMPLE SUMMARY: Cancer rates have been accelerating significantly in recent years. Despite notable advances having been made in cancer therapy, and numerous studies being currently conducted in clinical trials, research is always looking for new treatment. Novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators, including chromatin modifiers, such as DNA methyltransferase and histone deacetylases, and microRNA. Combinatorial treatments have several advantages: they enhance viral entry, replication, and spread between proximal cells and, moreover, they strengthen the immune response. In this review we summarize the main combination of therapeutic approaches, giving an insight into past, present, and future perspectives. ABSTRACT: According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).