X-ray beams could kick start genes into fighting cancer as an exciting new way of targeting therapy against the disease, according to new research in the Journal of Gene Medicine1.
Cancer Research UK scientists have successfully used gene therapy to enhance the effects of radiotherapy and to encourage cancer cells to commit suicide. By using a new type of ‘switch’ – activated by a precise X-ray beam pointed at cancer cells – they ensured the treatment affected only cancer cells and not normal ones.
The team now plans to test the results in patients through a clinical trial.
Researchers Professor David Hirst, Dr Jenny Worthington and Dr Tracy Robson – working at the University of Ulster in Newtownabbey and funded by Cancer Research UK – used gene therapy to increase the amount of a molecule called nitric oxide in tumour cells.
In addition to performing a range of important functions in the body, nitric oxide can kill cancer cells. Nitric oxide can also enhance radiotherapy by mimicking oxygen, optimal levels of which are normally required in cancer cells for radiotherapy to work.
Dr Worthington, who led the research, says: “We delivered a gene to tumours that encourages cells to make nitric oxide. The gene had a switch attached so we could turn it on only in cancer cells, which is important because enhancing nitric oxide production throughout the body could be dangerous. Our strategy avoids that.”
The switch they used is called the WAF1 promoter and can be turned on using the precisely directed X-ray beam used routinely in radiotherapy. The team tested the technique on bowel and fibrous tissue2 tumours in the laboratory to see if the gene therapy enhanced the effect of radiotherapy on those tumours.
They measured their results by monitoring how effectively the gene therapy – combined with radiotherapy – delayed growth in the tumours.
Cancer Research UK’s Professor David Hirst, who leads the research team, says: “We saw up to a two-fold increase in the effectiveness of radiotherapy on tumours. That means doctors could achieve the same radiotherapy benefit using much less radiation than they would otherwise use, so reducing the side effects of treatment.
“Alternatively, they could use the same dose of radiation and kill more cancer cells.”
The researchers also measured the amounts of nitric oxide in both cancerous and normal cells to see how well they had been able to target the gene therapy. Encouragingly, they found that production of the molecule had only been enhanced in tumour cells and the cells immediately surrounding them.
Professor Hirst adds: “Many scientists researching gene therapy use viruses to deliver genes to cells. We tried a different approach – using tiny spheres of lipid called liposomes, which interact in a natural way with the lipids in a cell’s membrane. Each method of delivery has advantages and disadvantages and extensive research on each will tell us which will work best in patients.”
Hirst and his team believe that the technique will be ready for testing in patients after some further refinement. They are also testing whether the technique enhances chemotherapy as well as radiotherapy.
Professor Robert Souhami, Cancer Research UK’s Director of Clinical and External Affairs, says: “Cancer is a complex disease and we need imaginative approaches to combat it. Using a switch turned on with a precisely directed x-ray beam is one such approach, and holds promise in targeting treatment towards cancer cells and avoiding healthy cells.
“Cancer Research UK is researching a wide range of gene therapies in order to harness the technique’s full potential against cancer.”
- Journal of Gene Medicine6 (6)
- Fibrosarcomas: a type of soft tissue sarcoma or tumour originating in the fibrous tissue which holds bones, muscles, and other organs in place.
Gene therapy means the use of genes in the treatment of disorders or diseases in the body. In studies of gene therapy for cancer, researchers are trying to improve the body’s natural ability to fight the disease or to make cancer cells more sensitive to other kinds of treatment.
The team used gene therapy to deliver a gene for the enzyme nitric oxide synthase (iNOS) to cancer cells. iNOS causes cells to make nitric oxide.
The gene construct – consisting of the gene and the WAF1 promoter – remains in body cells for approximately one week after delivery.