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In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment\u2010resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>\n                      Combination\u2010based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have been widely investigated to further improve anti\u2010tumour efficacy. These approaches act through complementary and synergistic mechanisms, where chemotherapy can promote viral replication and increase tumour cell susceptibility through deoxyribonucleic acid (DNA) damage and transient immunomodulation, while radiotherapy enhances immunogenic tumour cell death by inducing sustained DNA damage. In parallel, immunotherapy\u2014particularly immune checkpoint inhibition\u2014can strengthen anti\u2010tumour immunity by reversing T\u2010cell exhaustion and increasing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell infiltration and effector function. Collectively, these interactions amplify both direct viral oncolysis and immune\u2010mediated tumour clearance. Additionally, clinical trial data suggest that intravenous administration of oncolytic adenoviruses may provide greater systemic antit\u2010umour activity compared with intratumoural delivery, albeit with increased toxicity relative to localised injection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oncolytic adenoviruses have emerged as promising treatment options for advanced and treatment\u2010resistant malignancies, particularly when integrated with chemotherapy, radiotherapy or immunotherapy. However, most studies included are early\u2010phase trials conducted in small patient cohorts, underscoring the need for further research to better define safety profiles, long\u2010term adverse effects, and the underlying mechanisms driving therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70702","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T07:25:23Z","timestamp":1779521123000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7939-0086","authenticated-orcid":false,"given":"Vlad","family":"Iova","sequence":"first","affiliation":[{"name":"Faculty of Medicine \u2018Carol Davila\u2019 University of Medicine and Pharmacy Bucharest  Bucharest 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