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New alliance for discovery of WNT pathway inhibitors to be used in cancer therapy

Cancer Research Technology, Merck Serono, Cancer Research UK, Cardiff University and The Institute of Cancer Research are set to begin a new research collaboration that will provide substantial investment in research on the WNT signalling pathway in the hope of finding new drug targets.

The cross-disciplinary, multicentre collaboration, which could span up to three years, will focus on the discovery of inhibitors of the WNT pathway. This pathway is involved in physiological tissue development in embryos, as well as in tissue maintenance in adults.

Mutations in the WNT pathway alter the molecular switches that regulate it and leave the pathway permanently switched on. Such continuous activation can result in the development of cancer. Deregulation of this pathway is a frequent activating event in human cancers and is known to be linked to bowel, skin, breast and other cancers. The aim of this collaboration is to identify and develop small-molecule inhibitors of the WNT pathway that could eventually become novel treatments for cancer patients.

Professor Trevor Dale, lead scientist on the programme at Cardiff University, said: ’Normal cells communicate with each other by exchanging WNT protein signals. A WNT signal will instruct a cell to grow, divide and behave like a stem cell. Cancer mutations break the molecular switches that connect WNT proteins to cell growth. This in effect leaves the pathway permanently switched on. This collaboration will allow us to convert these biological insights into therapies which one day may help us treat cancer patients.’

The WNT pathway derives its name from the Drosophila (fruit-fly) Wingless gene and the mouse INT-1 gene. WNT ligands are key regulators of cell reproduction development and survival. They mediate a range of processes, including regeneration and injury repair in adult tissues. This involves regulating a number of biochemical signalling pathways.

Further information
For more information, see Dale, T. et al. (2008) The potential for targeting oncogenic Wnt/β-catenin signaling in therapy. Current Drug Targets 9, 532–547.


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