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

Jul 15 2009

Cancer Research Technology (CRT), Merck Serono, a division of Merck KGaA, Darmstadt, Germany, Cancer Research UK, Cardiff University and The Institute of Cancer Research (ICR) are set to begin a major new research collaboration for the first time. This will provide substantial investment in research on the WNT signalling pathway in the hope of finding new drug targets.

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

Mutations in this pathway alter the molecular switches that regulate the WNT pathway and leave it 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.

This collaboration was established by CRT, Cancer Research UK's commercialisation and development company, following work funded by the charity's Discovery Committee which set the translational foundations for the programme.

Merck Serono will contribute substantial funding which will augment existing investment by Cancer Research UK, the ICR and Cardiff University. This will allow more rapid translation of insights into drugs that may benefit cancer patients. The work will take place at Cardiff University, the ICR and Merck Serono. Financial details were not disclosed.

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."

Professor Julian Blagg, the lead scientist at The Institute of Cancer Research continued: "This collaboration brings together Cardiff's expertise in the fundamental biology of the pathway along with the drug discovery and development expertise at the ICR and Merck Serono. This will enable us to make real progress in targeting this exciting area and harness the enormous potential in WNT pathway therapy."

Dr Phil L'Huillier, CRT's director of business management, said: "Today's deal represents a significant endorsement for investment in the development of early scientific research. It is testament to the promise of the lab-based research that we are now in a position to take it forward with such a large-scale project and begin to think about new treatments for cancer patients. We hope by pooling expertise we will be able to progress WNT pathway inhibitors in the fastest possible time."

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 reference: Trevor Dale et al. 2008. Ewan, K. and Dale, T. C. (2008) Page 532 to 547. The potential for targeting oncogenic WNT/β-catenin signaling in therapy. Current Drug Targets 9 (7).