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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Cancer Research UK
- Cancer Research UK’s vision is to conquer cancer through world-class research.
- The charity works alone and in partnership with others to carry out research into the biology and causes of cancer, to develop effective treatments, improve the quality of life for cancer patients, reduce the number of people getting cancer and to provide authoritative information on cancer.
- Cancer Research UK is the world’s leading independent charity dedicated to research on the causes, treatment and prevention of cancer.
- For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit Cancer Research UK
The Paterson Institute for Cancer Research
- The Paterson Institute is part of the newly launched Manchester Cancer Research Centre at The University of Manchester.
- Research spans the whole spectrum of cancer research, from programmes investigating the molecular and cellular basis of cancer to those focused on translational research and the development of novel therapeutic approaches.
- Facilities include micro-arrays, advanced imaging, bioinformatics and state-of-the-art mass-spectrometry based proteomics.
- The institute has over 200 postdoctoral scientists, clinical fellows, scientific officers, administrative and technical staff, postgraduate research students and visiting fellows.
- For more information please visit www.picr.man.ac.uk
The Journal of Gene Medicine is the official journal of the European Society of Gene Therapy, the Japan Society of Gene Therapy and the Australasian Gene Therapy Society. The journal publishes articles on the science of gene transfer and its clinical applications. See The Journal of Gene Medicine website.
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