Strategic Combinations: The Future of Oncolytic Virotherapy with Reovirus

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...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2016-05, Vol.15 (5), p.767-773
Main Authors: Zhao, Xing, Chester, Cariad, Rajasekaran, Narendiran, He, ZhiXu, Kohrt, Holbrook E
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Combined Modality Therapy
Genetic Vectors - genetics
Humans
Immunotherapy
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - therapy
Oncolytic Virotherapy
Oncolytic Viruses - physiology
Radiotherapy - methods
Reoviridae - physiology
Signal Transduction
Virus Replication
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Summary: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.
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-15-0695