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Review
. 2018 Jun 14:7:53-63.
doi: 10.2147/OV.S143808. eCollection 2018.

Current understanding of reovirus oncolysis mechanisms

Matthew B Phillips  1 , Johnasha D Stuart  1 , Roxana M Rodríguez Stewart  2 , Jameson Tl Berry  2 , Bernardo A Mainou  2 , Karl W Boehme  1
Affiliations
Review

Current understanding of reovirus oncolysis mechanisms

Matthew B Phillips et al. Oncolytic Virother. .

Abstract

Mammalian orthoreovirus (reovirus) is under development as a cancer virotherapy. Clinical trials demonstrate that reovirus-based therapies are safe and tolerated in patients with a wide variety of cancers. Although reovirus monotherapy has proven largely ineffective, reovirus sensitizes cancer cells to existing chemotherapeutic agents and radiation. Clinical trials are underway to test the efficacy of reovirus in combination with chemotherapeutic and radiation regimens and to evaluate the effectiveness of reovirus in conjunction with immunotherapies. Central to the use of reovirus to treat cancer is its capacity to directly kill cancer cells and alter the cellular environment to augment other therapies. Apoptotic cell death is a prominent mechanism of reovirus cancer cell killing. However, reoviruses can also kill cancer cells through nonapoptotic mechanisms. Here, we describe mechanisms of reovirus cancer cell killing, highlight how reovirus is used in combination with existing cancer treatments, and discuss what is known as to how reovirus modulates cancer immunotherapy.

Keywords: cancer; cell death; immunotherapy; interferon; virotherapy.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic representation of the reovirus virion. The outer capsid (µ1 and σ3), core (black), and attachment protein σ1 are indicated. The λ2 protein is shown in gray. The 10 segments of viral genomic RNA are shown in white.
Figure 2
Figure 2
Effect of Ras transformation on reovirus oncolysis. In normal cells, viral dsRNA is recognized by PKR, triggering its auto-phosphorylation and activation. Activated PKR phosphorylates eIF2α resulting in inhibition of protein synthesis. In Ras-transformed cells, viral uncoating during cell entry is enhanced by higher levels of cathepsins, viral protein synthesis is boosted by Ras inhibition of PKR, and programmed cell death is impaired. Ras also stimulates growth and survival of tumor cells. Signaling through EGFR can also activate Ras and enhance the oncolytic effects of reovirus.
See this image and copyright information in PMC

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