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Last Updated: Thursday, 19 February, 2004, 00:18 GMT
Cancer 'bouncers' keep drugs out
Breast tumour
Scientists have discovered cancer cells have a team of 'bouncers' which can prevent drugs from attacking tumours.

A complex defence system includes 'doormen' molecules which throw out chemotherapy drugs, according to a European Journal of Cancer study.

Researchers were able to knock out the bouncer molecules, allowing treatment to get through.

And a study in Nature showed cancer cells squash blood and lymphatic blood vessels to stop drugs reaching tumours.

Both studies should help scientists understand more about how to beat cancer cells' defence systems.

'Hostile environment'

Cancer Research UK scientists at Oxford's John Radcliffe Hospital looked at how they could prevent the 'bouncer' molecule - P-glycoprotein - from blocking the action of chemotherapy drugs in cancer cells.

It raises the possibility of new types of treatment to overcome a tumour's resistance to chemotherapy
Dr Richard Callaghan, John Radcliffe Hospital
They knew a drug called XR9576 could block P-glycoprotein and sensitise individual cancer cells to chemotherapy, but they did not know if the drug would be successful against whole tumours, which can be very difficult to treat.

To see if the treatment could be effective, they grew balls of cancer cells in a laboratory, some with low amounts of P-glycoprotein, and others with high.

The tumours were treated with two common components of chemotherapy - vinblastine or doxorubicin.

Tumours with low amounts of P-glyoprotein were highly sensitive to both drugs.

But those with high P-glycoprotein were up to 20 times more resistant to doxorubicin and up to 300 times more resistant to vinblastine.

The researchers then repeated the test, pre-treating the tumours with XR9576 which stripped the tumours of resistance to chemotherapy, making them far more sensitive to treatment.

Dr Richard Callaghan, who led the study at the John Radcliffe Hospital, University of Oxford, says: "The core of a tumour is an extremely hostile environment for anti-cancer drugs to work in, with a variety of barriers put up to stop drugs from taking effect.

"What we were able to show in this study was that P-glycoprotein is not only a key player in drug resistance, but that we can do something to counter the problem, by knocking out the molecule's action.

"It raises the possibility of new types of treatment to overcome a tumour's resistance to chemotherapy."

Pressure relief

In a second study, carried out by researchers at Massachusetts General Hospital, Boston, researchers found cancer cells also act like a foot on a hosepipe stopping water.

The cells themselves squash the blood and lymphatic vessels which supply them to block the progress of anti-cancer drugs.

The researchers said the finding could explain why some treatments did not work as well as they should.

Scientists implanted human tumours into mice, then gave a dose of diphtheria, which is toxic to human tissue, but not to mice.

Diphtheria killed the cancer cells, relieving pressure on vessels.

However, while treated blood vessels appeared to be functioning almost normally, treated lymphatic vessels were not functional

But the scientists, led by Professor Rakesh Jain, said while opening blood and lymph vessels could improve the delivery of drugs, it could also provide an escape route for spreading cancer cells.

Dr Julie Sharp, senior science information officer at Cancer Research UK, said: "Cancer cells put pressure on the local blood vessels, making it harder for ant-icancer drugs to reach their target.

"These findings could pave the way for approaches to improve the delivery of drugs to cancer cells in the future."

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