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Gene therapy shield for cancer treatment

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by Cancer Research UK | News

27 February 2006

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Gene therapy could be used to shield important healthy stem cells of cancer patients during radiotherapy, enabling stronger doses to be administered safely, according to a report published today in the Journal of Gene Medicine*.

Many of the damaging side effects of radiotherapy result from the death of bone marrow cells, the producers of blood cells vital for life. The new technique makes the marrow stem cells produce more of a protein called SOD2**, which protects against the mechanisms that lead to cell death from radiation.

Scientists at The University of Manchester’s Paterson Institute for Cancer Research, funded by Cancer Research UK, have proved that this strategy reduces the effects of radiation treatment on healthy bone marrow stem cells in the lab, and are looking to develop the principle further. They hope their work will eventually lead to a pre-treatment that protects bone marrow from the unwanted side effects of radiotherapy treatment.

Such a protective effect would allow doctors to use higher doses of radioactive components, such as newer treatments that take radioactive substances straight to cancer cells, making these therapies better at killing cancer cells. Although the work is certainly some way from clinical use, the science so far is promising.

Radiation generates highly reactive chemicals, called free radicals, inside the body. These cause damage to DNA in cells. If the damage cannot be repaired by the cell, the cell dies. Radiation is therefore a useful therapeutic tool for killing cancer cells. But the big problem is to avoid damaging the body’s normal, healthy cells.

Cells have developed their own way of protecting against this sort of damage. A family of molecules called superoxide dismutases (SOD) are able to convert some free radicals into hydrogen peroxide, which can then be disposed of by the cell.

Study scientist Dr Thomas Southgate says: “We wanted to see if we could raise the level of protection available to normal human bone marrow cells by boosting the amount of SOD2, one member of the SOD family, that they produce. We used a harmless virus to insert an extra copy of the SOD2 gene into the stem cells that were then bombarded with radiation to gauge the effect.”

The bone marrow stem cells with an extra copy of SOD2 were able to continue to proliferate at doses of radiation that would normally kill unprotected cells, proving that the extra gene bestowed significant protection from the effects of radiation.

Dr Southgate adds: “Our results show that this treatment approach could have a substantial radioprotective effect to the human bone marrow, reducing the killing of healthy cells, making radiotherapy more effective.

“There is still a great deal of work to be done before we can start trying it in patients but the prospects are potentially very exciting.”

Dr Lesley Walker, Cancer Research UK’s Director of Cancer Information, says: “There is always room to improve existing treatments for cancer. Radioprotective gene therapy, as described in this study, would enhance the effectiveness of many types of radiation treatment currently used for treating cancer.”


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