Scientists discover how to activate genetic 'switch' that stops cancer

A way of ridding the body of lethal tumours has been identified by scientists who have used a genetic "switch" to turn on a key gene for suppressing cancer.

The findings suggest there may be a way of re-activating a damaged gene that is normally involved in the natural suppression of the uncontrolled cell division that leads to cancer.

In a study on laboratory mice, the scientists demonstrated that it was possible to arrest the growth of tumours by activating the p53 gene, which is known to be involved in cancer suppression. In some of the animals the tumours shrank by between 40 and 100 per cent and the experimental technique appeared to work on two quite different kinds of cancer that are also known to affect humans.

It is well established that the p53 gene for tumour suppression is mutated in more than half of all human cancers - indicating that it plays a critical role in triggering the onset of the disease.

The findings of the latest study, published in the journal Nature, suggest that it may be possible to develop new drugs that are able to reactivate damaged p53 genes to cause tumours to disappear.

"If we can find drugs that restore p53 function in human tumours in which this pathway is blocked, they may be effective cancer treatments," said David Kirsch of the Massachusetts Institute of Technology and Harvard Medical School in Boston.

The scientists said a few compounds were known to restore the function of the p53 gene but until now it had not been known whether such activity would actually reverse the growth of tumours in primary cancers - those that have not yet spread to other parts of the body.

In the study, genetically modified mice with the p53 turned off were given treatment that turned the gene on again after they had already developed tumours. Once the genetic switch was activated, the majority of the tumours shrank by between 40 and 100 per cent.

The scientists investigated lymphomas, cancers of the blood, and sarcomas, cancers of the connective tissue, and they observed improvements in both cases, albeit in different ways.

In the lymphomas, the cancer cells underwent a natural process of cell "suicide" called apoptosis within a couple of days of p53 activation. In the sarcomas, the tumours stopped growing and were gradually cleared away, although the shrinking process was slower than for the lymphomas.

Scott Lowe, deputy director of Cold Spring Harbor Laboratory's Cancer Centre in New York, a member of the research team, said that the findings may lead to new ways of treating patients suffering from cancers that are resistant to other forms of treatment. "This suggests that targeted therapies that act to reactivate tumour suppressors may be an effective new strategy to treat resistant cancers," Dr Lowe said.

Andrea Ventura, a scientist at MIT who was part of the research team, said the findings underscored the important role that p53 plays in blocking the uncontrolled proliferation of cancer cells.

"This study provides critical genetic evidence that continuous repression of a tumour suppressor gene is required for a tumour to survive," Dr Ventura said.

The study also demonstrated that the reactivation of the p53 gene within the tumour cells did not affect normal, healthy cells - indicating the low probability of damaging side effects.

"This means you can design drugs that restore p53 and you don't have to worry too much about toxic side effects," Dr Ventura said.

Further research is needed before the findings can be applied to patients. One class of substances under study as potential new drugs are called nutlins, which interfere with an enzyme that keeps levels of p53 low.