Compounds may disrupt tumour cell growth

In collaboration with the Press Association

UK researchers have identified four compounds that appear to be able to block tumour cell growth in the laboratory.

The four compounds interfere with a particular chemical messaging system, called the 'Wnt' pathway, which has previously been found to be involved in cancer development.

Dr Trevor Dale, a Cancer Research UK-funded biochemist based at Cardiff University, has shown that the compounds can block tumour cell growth in zebrafish embryos and now hopes to test them on mice.

Reporting the team's findings at an international conference in Germany on 'Wnt Signalling in Development and Disease', the researchers revealed that interfering with the Wnt signalling pathway can have severe side-effects, as it plays a central role in living organisms.

In addition, the kinds of drugs needed to interfere with the pathway are hard to develop, according to Dr Dale: "Drugs that inhibit easy targets, such as enzymes, can be developed by testing likely compounds on purified enzymes. The drugs usually fit into small pockets on the enzyme like a broken key fitting into a lock and preventing the normal key from getting access.

"Drugs that inhibit hard targets, such as protein-protein interactions, are more difficult to develop since they usually don't have small pockets. Most 'core' targets of the Wnt pathway fall into this class."

The researchers identified the four compounds by screening 68,000 for their ability to disrupt the Wnt pathway.

Dr Dale revealed: "Once the active compounds were identified, we were then faced with the problem of identifying the targets of the pathway."

They found that two of the compounds block the pathway near a protein called beta-catenin.

As a result, they now plan to use variants of the compounds to try and block bowel cancer development in mice, as beta-catenin regulates the activity of another protein, APC, which is involved in 90 per cent of bowel cancers.

Depending on the results of the study, the researchers may subsequently be able to move on to clinical trials in the future.