Raquel Yokoda, Bolni M Nagalo, Mansi Arora, Jan B Egan, James M Bogenberger, Thomas T DeLeon, Yumei Zhou, Daniel H Ahn, Mitesh J Borad

Upper gastrointestinal tract malignancies are among the most challenging cancers with regard to response to treatment and prognosis. Cancers of the esophagus, stomach, pancreas, liver, and biliary tree have dismal 5-year survival, and very modest improvements in this rate have been made in recent times. Oncolytic viruses are being developed to address these malignancies, with a focus on high safety profiles and low off-target toxicities. Each viral platform has evolved to enhance oncolytic potency and the clinical response to either single-agent viral therapy or combined viral treatment with radiotherapy and chemotherapy. A panel of genomic alterations, chimeric proteins, and pseudotyped capsids are the breakthroughs for vector success. This article revisits developments for each viral platform to each tumor type, in an attempt to achieve maximum tumor selectivity. From the bench to clinical trials, the scope of this review is to highlight the beginnings of translational oncolytic virotherapy research in upper gastrointestinal tract malignancies and provide a bioengineering perspective of the most promising platforms.