Cardiff: New hits found to interrupt cancer pathway

Researchers at Cardiff University in the UK have used new insights into the Wnt cell signalling pathway to discover potential new anticancer compounds.

Working from a library of 68,000 compounds, biochemist Trevor Dale and colleagues have identified four which stop Wnt signaling and thus block tumor cell growth in cell culture and zebrafish embryos. Dale now plans to test the compounds in mouse models. He described his work at the recent conference “Wnt Signaling in Development and Disease”, at the Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.

Researchers face two major problems in trying to block Wnt signalling. First, due to its central role in living organisms, interfering with the pathway can cause severe side effects.

The second issue is that the core components of the Wnt pathway are hard to target, according to Dale. “Drugs that inhibit easy targets, such as enzymes, can be developed through standard screening approaches using purified enzymes.

“Drugs that inhibit hard targets, such as protein-protein interactions, are more difficult to develop […and most] of the core targets of the Wnt pathway fall into this class.”

In future studies, Dale and his co-workers want to use variants of their four compounds in mouse models of colon cancer, paving the way for human studies.