Oncolytic viruses: A novel therapeutic approach for pancreatic cancer

Pancreatic cancer, particularly the exocrine-type pancreatic ductal adenocarcinoma, has a dismal prognosis, with a 5-year survival rate of only 2%-9%, depending on the geographic region. The high aggressiveness of this malignancy is attributed to factors such as late diagnosis, an immunosuppressive and desmoplastic tumor microenvironment, early metastasis, and resistance to conventional therapies. Even novel immunotherapies such as immune checkpoint inhibitors have shown little efficacy in clinical trials. Surgical resection is the only potentially curative treatment; however, few patients are eligible for surgery at diagnosis, and the recurrence rates are quite high. Recently, oncolytic viruses have emerged as promising alternatives for treating this disease. Oncolytic viruses selectively infect, replicate, and lyse cancer cells, triggering immunogenic cell death and initiating antitumor immune responses, offering a potential strategy to overcome the immunosuppressive tumor microenvironment. Additionally, oncolytic viruses can be genetically engineered to enhance tumor selectivity and antitumor immunity, providing increased safety and efficacy. This review aims to characterize oncolytic viruses and pancreatic ductal adenocarcinoma, explore the current state-of-the-art research on oncolytic virotherapy for treating this disease, and provide a summary of ongoing and completed clinical trials. Furthermore, the challenges of oncolytic virotherapy in pancreatic cancer have been highlighted, along with future perspectives for advancing this field.