Infecting Cancer with a Virus

DNA repair via XRCC2 and XRCC4 silenced with lentivirus RNA interference

(RxWiki News) Cancer cells divide quickly, meaning that their genetic material is unprotected more often than normal cells. Radiation therapy targets the tumor to increase mutations, damaging the tumor cells to the point of killing the cell.

A group of scientists studied the mechanics of how to use a virus to weaken DNA repair, making the tumor cells even more vulnerable to radiation. This would allow oncologists to use lower doses of radiation, lessening the chance of skin rashes and damage to healthy tissues.

"Ask your oncologist about retroviral therapy."

Researchers from the Winship Cancer Institute led by Ya Wang, M.D., PH.D., developed specialized viruses, a distant and heavily modified cousin of the HIV virus, which would introduce genetic material permanently into the cell's DNA. Viruses from the lentivirus family have been used for years in experiments to introduce new genes into cells.

The hope is that the virus can be engineered to target only cancer cells. The virus attempts to target a signal produced by two genes more active in tumor cells known as XRCC2 and XRCC4.

The virus then uses the principle of RNA interference to silence these two genes, making the coding process unstable and shutting down error repair entirely. This has the effect of making cancer cells up to three times as sensitive to radiation therapy.

The subject of the 2006 Nobel Prize in Medicine, RNA interference has been an experimental technique only used in the laboratory, but with further development of the virus, this could be used as a therapy in clinical trials.

"Inhibition of DNA repair has been tried using drugs that inhibit repair enzymes," Dr. Wang said. "This approach -- combining targeted genes and combining targeted regions of one gene -- made it possible to efficiently knock down either gene and achieve a greater sensitivity to radiation."

This potential route of therapy has not yet been tested outside of an experimental laboratory setting.

The results are published in the March 1, 2012 issue of Cancer Research.

Financial disclosure for this research was not made publicly available.

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Review Date: 
March 26, 2012