Harnessing the power of oncolytic viruses for advancing cancer therapy

Abstract

• Oncolytic viruses were previously viewed solely as harmful pathogens, but are now powerful, genetically engineered tools for cancer therapy. They represent a rapidly advancing, promising component of multimodal cancer treatment. In this review, the oncolytic effect of both natural and modified viruses, such as adenovirus, herpes simplex virus, reovirus, vaccinia, Newcastle disease virus, and canine distemper virus reported by deferent researcher has been included. • This review addresses different mechanisms by which oncolytic viruses act: direct tumor lysis, disruption of tumor vasculature, and stimulation of innate and adaptive immune responses. It also provides a comprehensive review of genetic engineering approaches of oncolytic viruses for increasing the safety, tumor targeting, and therapeutic potency through virulence attenuation, promoter-based targeting, miRNA-based translation control, and insertion of therapeutic genes, including anti-angiogenic factors, immunomodulators, and prodrug-converting enzymes. • Virotherapy challenges, including immune clearance, physical barriers in the tumor microenvironment, and immunosuppression of the tumor, are addressed in this review. To overcome these challenges, combination of virotherapy with immune checkpoint inhibitors, radiation, or chemotherapy shown synergistic results in different preclinical and clinical test are also reviewed in this article. Oncolytic viruses are a novel and promising approach to cancer treatment. These viruses are either naturally occurring or genetically engineered to target and kill cancer cells while sparing healthy tissue. A growing body of research and clinical achievements is bolstering the use of oncolytic viruses. Adenoviruses, measles viruses, herpes simplex virus, and vaccinia viruses are some of the major oncolytic viruses used in cancer treatment. Oncolytic viruses function through different mechanisms: direct killing of tumor cells, immunological activation, and remodeling of the tumor microenvironment. Advancements in genetic engineering make oncolytic viruses a powerful anti-cancer tool by enhancing their tumor-specific targeting, reducing their pathogenic effects, and using viruses as vectors for expressing various therapeutic transgenes. Despite this promise, challenges such as tumor heterogeneity, physical barriers, immune clearance, and the immunosuppressive tumor environment can limit their effectiveness. This complexity necessitates combination therapies to improve OV efficacy and overcome tumor resistance. This article provides a comprehensive update on oncolytic viruses, genetic modification to enhance virotherapy, alongwith the hurdles and potential prospects for integrating this approach with existing cancer treatments.