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Potential new drugs to help both cancer and diabetes patients

With Worldwide Cancer Research funding, scientists have created new molecules that they hope can become drugs for both cancer and diabetes. Their findings are published this week in the Journal of Medicinal Chemistry.

The chemical compounds reduce the growth and proliferation of colon (bowel) cancer cells, and increase glucose uptake into fat cells meaning they could also help diabetes patients manage their disease.

The research team from Cancer Research at Bath (CR@B), working with colleagues at the University of Oulu in Finland, designed and made two molecules to specifically stick to and switch off enzymes called tankyrases, which are involved in an important cellular process called Wnt/β-catenin signalling.

Nearly all bowel cancers, and several other cancers, are encouraged to grow through a malfunction of the Wnt signalling system, where it is permanently switched “on”, like a foot on an accelerator. As the enzyme tankyrase is an important part of the Wnt system, the researchers realised switching it off could block the Wnt/β-catenin signalling pathway, like taking the foot off the accelerator, and stop the bowel cancer cells from growing. High levels of Wnt/β-catenin signalling is also observed in many inflammatory diseases including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In lab experiments their custom built tankyrase inhibitors significantly reduced Wnt/β-catenin signalling and slowed down growth and proliferation of bowel cancer cells.

They also showed that targeting tankyrases results in increased uptake of glucose into fat cells. Potent and selective inhibition of tankyrases could therefore also be useful for patients with Type II diabetes to help manage their disease, and possibly reduce the amount of insulin administered to patients with Type I diabetes.

Dr Amit Nathubhai, from the University of Bath’s Department of Pharmacy and Pharmacology, said: “It’s early days but our new set of molecules are a great starting point towards the development of new drugs that target the tankyrases and Wnt signalling to treat cancer, diabetes and inflammatory diseases.

“We have shown they are potent and selective and we see enhanced glucose uptake and a marked reduction of bowel cancer cell proliferation using our molecules.

“The next phase of our research is to further optimise our molecules and evaluate them further in other biological models of diabetes and obesity. We hope to reveal the underlying mechanism(s) that link cancer, fibrosis, diabetes and obesity, which remains unclear.”

The team plan to develop 3D models using cells from patients with diseases such as bowel cancer, prostate cancer, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis to better understand the effects their Tankyrase/Wnt signalling inhibitors may have on these conditions.

Better treatment of bowel and gastic cancers could benefit over 4,500 patients and save the NHS £24 million.

The research was funded by grants from Worldwide Cancer Research, Medical Research Council and the Academy of Finland.

This article was first published by the University of Bath.

Photo - The new molecules bind to tankyrase enzymes. Credit: Dr Lari Lehtiö