Strategic combinations: The future of oncolytic virotherapy with reovirus

Xing Zhao, Cariad Chester, Narendiran Rajasekaran, Zhixu He, Holbrook E. Kohrt

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)767-773
Number of pages7
JournalMolecular Cancer Therapeutics
Volume15
Issue number5
DOIs
StatePublished - May 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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