Emerging and Re‐Emerging Viral Pathogens in Oncolytic Virotherapy: A Comprehensive Review

ABSTRACT

Oncolytic virotherapy has recently emerged as a promising immuno‐oncological strategy, utilising the natural cytolytic potentials of viral pathogens to selectively target and destroy malignant cells. Although various engineered viruses, such as adenoviruses, vaccinia virus, and herpes simplex virus, are currently in clinical evaluation, emerging and re‐emerging viruses with intrinsic oncolytic potential, including Zika virus (ZIKV), Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), Dengue virus (DENV), and West Nile virus (WNV), have also shown promising results. These emerging and re‐emerging viral pathogens show specific tumour tropism, immune evasion strategies, and immunogenic cell death mechanisms that could be harnessed for next‐generation therapeutic platforms. Nonetheless, concerns related to safety, viral pathogenicity, host immune responses, and the risk of uncontrolled viral dissemination present significant translational challenges. The present review provides a comprehensive overview of novel viral candidates, including ZIKV, SARS‐CoV‐2, DENV, and WNV, in oncolytic virotherapy, their molecular mechanisms of tumour targeting, and current advancements in genetic engineering aimed at improving therapeutic efficacy and biosafety. Moreover, this review describes clinical perspectives, regulatory considerations, and future directions in integrating emerging virotherapeutic agents into precision oncology.