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Study Gives Better Understanding Of How Reoviruses And Chemo Work Together

Posted on: 13 May 10

Summary

Researchers at Weill Cornell Medical Center in New York have demonstrated that a reovirus therapy called REOLYSIN works synergistically with gemcitabine and may be worth further investigation.

Gemcitabine is part of a group of medications used in cancer treatment known as antimetabolites. Antimetabolites are very similar to naturally occurring chemicals in the body that cells use to build DNA and other important parts of the cell. Because cancer cells mistake them for the real chemicals to build their DNA, antimetabolite medications work by preventing cell growth and multiplication and may cause cancer cell death.


As effective as Gemcitabine is against some cancers, it has not been proven effective as a standalone treatment for eradicating certain other forms such as colon cancer. However, researchers at Weill Cornell Medical Center in New York have demonstrated that a reovirus therapy called REOLYSIN works synergistically with gemcitabine and may be worth further investigation.


REOLYSIN, a formulation of the human reovirus, does what viruses do best – they keep replicating until their host (the cell) is overwhelmed. Then they move on to the next cell. In REOLYSIN’s case, the host consists of as many as two-thirds of all cancers that share a common feature, called an “activated Ras pathway.” If the cancer cell has this Ras pathway, it is unable to fight off the REOLYSIN therapy, and the cancerous cells die.


The oncology team at Weill Cornell recently presented their findings at this year’s annual meeting of the American Association for Cancer Research. Their poster, titled "Molecular pathways associated with REOLYSIN and gemcitabine synergy in ras-mutated human HCT116 cells," covered preclinical work done to better understand the mechanisms associated with the cytotoxic synergies in this combined approach. The hope is that finding a better understanding of the synergy between the two therapies will allow physicians to better select drug combinations for specific tumors.


The investigators concluded that the top three canonical pathways significantly affected by the combination treatment were interferon signaling, antigen presentation and the protein ubiquitination pathways. Addressing these were key to battling hard-to-treat cancers.

These data suggest that the combination of gemcitabine and REOLYSIN stimulates the immune system to increase the surveillance and/or recognition of cancer cells. The researchers concluded that single-agent gemcitabine has proven to be inactive in colon cancer, yet HCT116 cancer cells treated with a combination of gem and REOLYSIN proved to be an effective preclinical therapy in these experiments. This enhanced preclinical efficacy is potentially due to an enhancement of tumor surveillance by the immune system.

“Understanding the mechanisms associated with synergy of these therapies will allow physicians to better select drug combinations for specific tumors,” said Brad Thompson, CEO of Calgary-based Oncolytics Biotech, which has provided REOLYSIN. “Clinical trials with REOLYSIN in combination with other chemotherapeutic drugs are ongoing,” he added. For more information, log on to www.oncolyticsbiotech.com

Janet Vasquez

Last updated on: 27/08/2010 11:40:18

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