Reovirus – pancreatic cancer’s natural enemy

Version française

Human reovirus type 3 Dearing (T3D) is a naturally occurring virus that can be used as a tumour specific oncolytic agent (figure 1). Infection by T3D is usually asymptomatic. It does not normally infect healthy cells. However it has been found that cancer cells with activated RAS pathway are readily infected and lysed [1]. KRAS is activated in 90% of the most common form of pancreatic cancer – ductal adenocarcinoma (PDAC). Therefore T3D is naturally selective for pancreatic cancer.

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Figure 1: 3D print of reovirus. Created by NIAID. No changes were made. Creative Commons Attribution 2.0 Generic.

When surgery is possible for pancreatic cancer the five year survival rate is around 22%. This indicates that recurrence is a large problem in pancreatic cancer. This is largely due to cancer stem cells which escape surgery and are highly resistant to chemotherapy. In fact chemotherapeutic agents for pancreatic cancer such a gemcitabine enrich for cancer stem cells [2]. One of the benefits of T3D and other oncolytic viruses is that they can infect slow proliferating cancer stem cells [3]. This a major benefit over small molecule inhibitors which are largely unable to destroy cancer stem cells due to high expression of drug efflux receptors, the cells slow proliferation and resistance to apoptosis. T3D has been shown to replicate in patient pancreatic tumour tissue and clinical trials are ongoing.

Refs

  1. Coffey, Matthew C., James E. Strong, Peter A. Forsyth, and Patrick W. K. Lee. ‘Reovirus Therapy of Tumors with Activated Ras Pathway’. Science 282, no. 5392 (13 November 1998): 1332–34. doi:10.1126/science.282.5392.1332.
  2. Sobrevals, Luciano, Ana Mato-Berciano, Nerea Urtasun, Adela Mazo, and Cristina Fillat. ‘uPAR-Controlled Oncolytic Adenoviruses Eliminate Cancer Stem Cells in Human Pancreatic Tumors’. Stem Cell Research 12, no. 1 (January 2014): 1–10. doi:10.1016/j.scr.2013.09.008.
  3. Marcato, Paola, Cheryl A Dean, Carman A Giacomantonio, and Patrick WK Lee. ‘Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells’. Molecular Therapy 17, no. 6 (June 2009): 972–79. doi:10.1038/mt.2009.58.
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