Oncolytic Viruses as a Novel Therapeutic Approach for Colorectal Cancer: Mechanisms, Current Advances, and Future Directions

This review provides an updated overview of oncolytic virotherapy as a promising therapeutic strategy for colorectal cancer (CRC), focusing on six key viral platforms: adenovirus, herpes simplex virus (HSV), reovirus, vesicular stomatitis virus (VSV), vaccinia virus (VV), and measles virus (MV). These viruses exhibit tumor-selective replication and exert their effects through mechanisms such as direct oncolysis, the delivery of immunostimulatory genes (e.g., IL-12, IL-15, GM-CSF), the activation of innate and adaptive immune responses, and the remodeling of the tumor microenvironment. Preclinical and early clinical studies suggest that oncolytic viruses can enhance the efficacy of existing treatments, particularly in immunologically "cold" tumors such as microsatellite stable CRC, when used in combination with chemotherapy or immune checkpoint inhibitors. Despite encouraging results, several challenges remain, including antiviral immune clearance, tumor heterogeneity, and limitations in systemic delivery. Current research focuses on improving viral engineering, enhancing tumor targeting, and designing combinatorial strategies to overcome resistance and maximize clinical benefits. Overall, oncolytic viruses represent a versatile and evolving therapeutic class with the potential to address unmet clinical needs in CRC.