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This unique attribute renders them valuable candidates for the development of anti-cancer therapeutics. The recognition of OVs dates to historical observations of tumor regression associated with systemic viral infections. Current advancements in technology enable us to harness this knowledge for therapeutic purposes. However, owing to their inherent pathogenic nature, OVs require genetic modifications to attenuate their virulence, heighten their specificity, and enhance their immunogenic properties. Within the scope of this review, we explore a range of strategies aimed at augmenting the therapeutic potential of OVs. Furthermore, we underscore the synergistic advantages achieved by combining OVs with other cancer treatment modalities. A detailed elucidation of the oncolytic mechanism executed by OVs is provided, and brief mentions are made regarding the positive outcomes observed in clinical trials involving selected OVs. Recent progress in oncolytic viral immunotherapy, exemplified by the utilization of non-infectious Plant virus-based Nanoparticles (PVNPs) in mammals and the application of the Zika virus in glioblastoma treatment, heralds a promising era for innovative therapeutic approaches in the battle against cancer.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12672-025-03973-3","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T13:56:11Z","timestamp":1764338171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A comprehensive review redefining viruses as therapeutic agents in cancer treatment"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1940-9663","authenticated-orcid":false,"given":"Anjana","family":"Jadhav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6684-3291","authenticated-orcid":false,"given":"Aravind","family":"J","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-602X","authenticated-orcid":false,"given":"Trupti","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"issue":"4","key":"3973_CR1","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1097\/00000441-190412740-00001","volume":"127","author":"G Dock","year":"1904","unstructured":"Dock G. 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