Efficacy of oncolytic viruses (OVs) in malignant tumor therapy: a review on its therapeutic aspects.

Despite the life-saving potential of mainstream cancer therapies like surgery, chemotherapy and radiation, the clinical effectiveness is often limited by systemic toxicity, a lack of specificity and the survival of resistant cancer stem cells. With a global cancer burden projected to exceed over 30 million new cases by 2050, oncolytic virotherapy has emerged as a significant development in cancer treatment. These viruses - either natural or genetically modified, selectively infect the cancer cells, replicate within them and destroy while sparing the healthy tissue. This review examines the therapeutic effectiveness and biological mechanisms of oncolytic viruses (OVs) as a modern approach to treating cancer aiming to discuss the engineered strategies that improve viral potency and safety, explore current clinical progress, and assess the potential of combination treatments. OVs mainly work through a two-pronged approach by direct killing or immunogenic cytolysis. By releasing tumor-specific antigens and pro-inflammatory signals, OVs change the cold tumor microenvironment into a hot one, drawing T-cells to attack both the main tumors and distant metastases. This review also explores key viral platforms, including the common viruses like the Adenovirus, Vaccinia virus, Herpes Simplex Virus (HSV-1) and Reovirus, across various cancers such as melanoma, glioblastoma and solid tumors. Clinical translation has advanced from anecdotal reports to over 250 active trials worldwide. While Imlygic remains a landmark FDA-approved treatment for melanoma, newer platforms like Delytact and H101 have received regional approvals. Key findings show that OVs are more effective when they are in synergy with immune checkpoint inhibitors like Pembrolizumab, that helps in achieving objective response rates (ORR) of up to 62% in advanced melanoma. However, challenges persist, including neutralization by host antibodies, physical barriers like high interstitial fluid pressure and scalability issues in manufacturing. Oncolytic virotherapy is now progressing to its next iteration, evolving from simple cytolytic agents to advanced programmable, biological platforms. Emerging trends, such as personalized neoantigen encoding and real-time monitoring with reporter genes, may help overcome existing delivery challenges. Integrating OVs with precision medicine and multimodal therapies is shaping the strategy for achieving durable clinical responses in the changing field of oncology.