The award is the fourth The Institute of Cancer Research (ICR) has received from the Wellcome Trust’s Technology Transfer division, which supports applied research and development projects to bridge the gap between fundamental research and commercial application.
Tankyrase inhibitors have been shown to halt growth in bowel cancer cells, demonstrating their potential as a promising approach for new cancer treatments.
Dr. Chris Lord and Professor Alan Ashworth of the ICR have pioneered the use of small molecule inhibitors of the PARP1 enzyme to target tumour cells, using a concept known as synthetic lethality. Over the past three years Dr. Lord and Professor Ashworth have used the same ideas to develop nanomolar IC50 small molecule inhibitors of a related PARP enzyme, tankyrase 1 (TNKS1).
The new funding from the Wellcome Trust will enable the ICR team to progress their programme towards developing a tankyrase inhibitor approved for patient use.
Drugs that can inhibit the enzyme tankyrase offer the opportunity to target one of the most common characteristics of cancer cells: the dependency on the Wnt signalling pathway.
Wnt signalling is commonly activated in bowel cancer. Chemical inhibitors of tankyrase have been shown to block Wnt signalling in bowel cancer, inhibiting the growth of tumour cells.
The Wellcome Trust award was made through their Seeding Drug Discovery initiative, a scheme which facilitates early-stage small-molecule drug discovery. Projects selected must address an unmet healthcare need and have a realistic prospect of being developed further by the pharmaceutical or biotechnology market.
Dr. Chris Lord, Senior Staff Scientist, Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, said: “Bowel cancer is the third most commonly diagnosed cancer in the UK, but despite its prevalence, survival rates remain relatively poor. The chances of a patient with bowel cancer surviving with their disease for longer than five years are not much greater than 50%, so more treatments are desperately needed.
“We know that oncogenic Wnt signalling is commonly activated in cancers, including bowel cancer, and tankyrase is one of the first well validated targets in Wnt signalling. This presents an exciting opportunity to target a range of tumours driven by Wnt signalling. Already, our team has developed some very potent and selective inhibitors of tankyrase. With the Wellcome Trust award we will be able to continue this work and hopefully turn these promising compounds into clinically useful drugs.
Professor Alan Ashworth FRS, Chief Executive Officer of The Institute of Cancer Research, said: “The development of tankyrase inhibitors illustrates how committed the ICR is to identifying more effective ways to treat cancer. This new funding from the Wellcome Trust is a significant boost to the world-leading drug discovery efforts already being carried out at the ICR.”