title: Strategic Combinations: The Future of Oncolytic Virotherapy with Reovirus.
abstract: The dominant cancer treatment modalities such as chemotherapy, radiotherapy, and even targeted kinase inhibitors and mAbs are limited by low efficacy, toxicity, and treatment-resistant tumor subclones. Oncolytic viral therapy offers a novel therapeutic strategy that has the potential to dramatically improve clinical outcomes. Reovirus, a double-stranded benign human RNA virus, is a leading candidate for therapeutic development and currently in phase III trials. Reovirus selectively targets transformed cells with activated Ras signaling pathways; Ras genes are some of the most frequently mutated oncogenes in human cancer and it is estimated that at least 30% of all human tumors exhibit aberrant Ras signaling. By targeting Ras-activated cells, reovirus can directly lyse cancer cells, disrupt tumor immunosuppressive mechanisms, reestablish multicellular immune surveillance, and generate robust antitumor responses. Reovirus therapy is currently being tested in combination with radiotherapy, chemotherapy, immunotherapy, and surgery. In this review, we discuss the current successes of these combinatorial therapeutic strategies and emphasize the importance of prioritizing combination oncolytic viral therapy as reovirus-based treatments progress in clinical development. Mol Cancer Ther; 15(5); 767-73. ©2016 AACR.
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California. Tissue Engineering and Stem Cells Research Center, Department of Immunology, Guizhou Medical University, Guizhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California. Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California. cchester@stanford.edu hzx@gmc.edu.cn.
authors.forename: Cariad
authors.initials: C
authors.lastname: Chester
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California.
authors.forename: Narendiran
authors.initials: N
authors.lastname: Rajasekaran
authors.affiliation: Tissue Engineering and Stem Cells Research Center, Department of Immunology, Guizhou Medical University, Guizhou, China. cchester@stanford.edu hzx@gmc.edu.cn.
authors.forename: ZhiXu
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California.
authors.forename: Holbrook E
authors.initials: HE
authors.lastname: Kohrt
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology; D011878:Radiotherapy / Q000379:methods; D012087:Reoviridae / Q000502:physiology; D015398:Signal Transduction; D014779:Virus Replication