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New drug could help target cancer cells with deadly accuracy

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by Cancer Research UK | News

28 October 2002

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A new drug that could revolutionise the impact of radiotherapy on cancer and make treatment much more effective, has been developed by Cancer Research UK scientists – it is announced today.

The drug, developed by the charity’s clinical unit at Newcastle University, has been designed to destroy the protection enjoyed by cancer cells.

Radiotherapy kills cancer cells by causing damage to DNA. But the DNA damage repair kit – the body’s Sir Lancelot which is present in all cells – rides to the rescue of the beleaguered cells and can get in the way of effective treatment.

The new drug will, in turn, disable the DNA repair process and allow radiotherapy to target tumours with deadly accuracy, according to research leader Professor Hilary Calvert, speaking at Cancer Research UK’s first annual conference in Kenilworth, Warwickshire.

Prof Calvert explains: “Our DNA is damaged all the time during life’s daily routine. One cell sustains about 30,000 incidents of DNA damage every day through the oxygen and chemicals circulating in the body. Therefore the DNA damage repair process is invaluable and keeps us from dissolving into a blob of jelly.”

But the downside of this is that the DNA repair kit also comes to the rescue of cancer cells when they are under attack. This has led scientists to search for a weapon to prevent the repair kit from working on tumours.

The most promising prospect in the armoury is a class of drugs known as PARP inhibitors which block the action of DNA repair enzymes called PARPs1. In pre-clinical studies researchers have found that these drugs are highly effective at sensitising cancer cells to radiotherapy.

Prof Calvert says that one of the problems with radiotherapy – which is the most common way of treating cancer apart from surgery – is that the dose needed to kill large tumours is often too toxic to be sustained by the body.

“We have been trying to find something to make tumours more sensitive to radiotherapy. And we hope the PARP inhibitor will prove an effective radiosensitizer which would be a huge benefit to cancer patients.

“Clinical trials of radiosensitizers have always posed a particularly difficult problem of design because we have to ensure that they are not increasing any side effects to normal tissue,” he says. “Many of the side-effects of radiotherapy are very late and can occur many months or years after the original treatment.”

Professor Robert Souhami, Director of Clinical Research for Cancer Research UK, says: “The development and production of the PARP inhibitors mean we have a potentially very exciting new approach to cancer treatment.

“But there is still much work to be done. We hope clinical trials will start soon but these would take several years to complete before any drug could be licensed for general use.”


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