Yokoda Raquel, Nagalo Bolni M, Arora Mansi, Egan Jan B, Bogenberger James M, DeLeon Thomas T, Zhou Yumei, Ahn Daniel H, Borad Mitesh J
Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ.
Department of Molecular Medicine, Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
Oncolytic Virother. 2018 Mar 23;7:13-24. doi: 10.2147/OV.S161397. eCollection 2017.
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.
上消化道恶性肿瘤在治疗反应和预后方面是最具挑战性的癌症之一。食管癌、胃癌、胰腺癌、肝癌和胆管癌的5年生存率很低，近年来这一比率的改善也非常有限。正在研发溶瘤病毒来应对这些恶性肿瘤，重点是高安全性和低脱靶毒性。每个病毒平台都在不断发展，以增强溶瘤效力以及对单药病毒疗法或病毒与放疗和化疗联合治疗的临床反应。一组基因组改变、嵌合蛋白和假型衣壳是载体成功的突破。本文回顾了每个病毒平台针对每种肿瘤类型的发展情况，试图实现最大程度的肿瘤选择性。从实验室到临床试验，本综述的范围是突出上消化道恶性肿瘤转化溶瘤病毒疗法研究的开端，并提供最有前景平台的生物工程视角。
