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Friday, September 10, 1999 Published at 00:29 GMT 01:29 UK


Health

Therapy 'cuts cancer side-effects'

Radiation treatment attacks healthy cells too

Researchers are developing a way to enable cancer patients who require follow-up treatment such as radiation or chemotherapy to avoid harsh side effects.

They believe this could be possible by shutting down a gene which tells normal cells to die at the end of their natural life cycle.

The finding turns current thinking on its head but carries the danger that it could leave the body vulnerable to another tumour.

Researchers at the University of Illinois in the US used drugs to stop a gene called p53 from working in mice and then gave them radiation treatment, which can have serious side effects.

But in the mice with the gene turned off, the side effects were greatly reduced, leading doctors to hope that in future they could use higher doses of radiation and improve cure rates.

Not an exact science

The p53 gene produces a protein which cells to die. It is absent in 60% of cancers, and therefore the cells contine to multiply out of control leading the formation of tumours.

At present surgery to remove tumours is accurate and can be targeted specifically at cancerous tissue.

But follow-up treatments such as radiotherapy attack all types of cell - healthy and cancerous alike - and so can lead to damaging side effects. Healthy cells, because they have the p53 gene, appear to be particularly vulnerable to cancer treatments.

Switching off the p53 gene appears to increase the chance that healthy cells will survive radiotherapy and chemotherapy.

"Inactivation of p53 has always been considered an unfavorable event," said Dr Andrei Gudkov, associate professor of molecular genetics at the university.

"But our approach was to temporarily and reversibly suppress p53 during radiation so that healthy cells would not self-destruct in response to damage from life-saving therapy."

Human use

The drug the researchers used to turn the gene off was called pifithrin, and they found that those mice who had taken it were protected from a radiation dose that would normally kill most of them.


[ image: Professsor Gordon McVie warned of the dangers]
Professsor Gordon McVie warned of the dangers
They hope to have the drug in the first stage of clinical testing within a year.

Professor Gordon McVie, director of the Cancer Research Campaign, said it was an extremely interesting piece of work but there were dangers attached to the approach suggested.

"The major concern is that it will produce tumours because the protein is one of the body's major defences against cancer," he said.

"You're opening the door to helping the cells become cancerous."

Other treatments

He said another question that would need to be addressed was whether or not switching off the p53 gene would encourage an already present tumour to grow faster.

However, the discovery could also lead to improved treatment in heart attacks and stroke, which are caused by blockages in blood flow.

"One of the first things that happens when you close down an artery is you activate p53, and it's p53 activation that causes a lot of the damage in the future, so it's a very neat idea and might have applications outside cancer," he said.

"But you'd have to make damned sure it didn't act as carcinogen."

The study was published in the journal Science.



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