Genetically engineering viruses to carry a suicide gene into ovarian cancer cells could become a potent way to tackle the disease, a leading Cancer Research UK scientist reveals at a conference in Glasgow today.
All normal cells have the gene, called Smac, switched on to trigger their own death when they reach a certain age. But cancer cells carry a faulty version of the gene and carry on dividing and growing well beyond their allotted lifespan.
Glasgow-born scientist, Dr Iain McNeish, will present his work on the Smac gene at the Cancer Research UK Beatson International Cancer Conference. He believes designing therapies to mimic or restore the function of Smac could effectively kill cancer cells by turning their self-destruct mechanism back on.
Dr McNeish’s team, based at the Cancer Research UK Molecular Oncology Unit in London, infected ovarian cancer cells with a modified virus carrying the gene for Smac and found that it caused large numbers of the cells to commit suicide.
They also discovered that the gene therapy could make ovarian cancer cells more sensitive to the chemotherapy drugs cisplatin and paclitaxel. The combination of Smac and either drug caused greater levels of cell death than the gene alone.
Dr McNeish says: “Previous studies have shown that Smac could enhance the effects of certain anti-cancer drugs. But our study is the first to show that the gene can be potent way to tackle cancer on its own as well as a complement to other treatments.
“Our latest research has also demonstrated that the delivery of the Smac gene with a virus has no effect on normal ovarian cells, and only seems to kill ovarian cancer cells. This is a very exciting result because it implies that the action of Smac may be tumour specific.”
Smac seems to make cells commit suicide by stopping the action of a molecule called XIAP, which is known to be vital for keeping cells alive. XIAP acts as a safety barrier stopping healthy cells from dying before their time is up.
Dr McNeish says: “Smac is too large to be delivered as an anti-cancer drug and developing synthetic versions that can be absorbed by cancer cells would require a huge effort in the pharmaceutical world. But sneaking the Smac gene into tumours using a virus could be an ideal way to overcome the problem.
“Our results indicate that developing a gene therapy to increase the levels of Smac in cancer cells may be a promising avenue to follow.”
Professor Robert Souhami, Director of Clinical Research at Cancer Research UK, says: “There is a real need to find innovative new ways to tackle cancer. This work exploits our knowledge of genes involved in cancer and targets a very specific molecular mechanism.
“There’s still work to do to find the best possible way of getting therapeutic genes into cancer cells, but over the coming decade we hope to see some exciting advances in this line of research.”