Bowel cancer protein study could lead to less toxic cancer drugs

X-ray showing colon cancer

Scientists have revealed the inner workings of a key protein involved in a wide range of cellular processes – potentially paving the way for better and less toxic cancer drugs. 

Using Nobel Prize-winning microscopy techniques, the researchers revealed how the tankyrase protein switches itself on and off by self-assembling into 3D chain-like structures. 

Their study, published in the journal Nature, reveals crucial structural insights into the elusive but important protein, which plays a particularly important role in helping drive bowel cancer. 

Scientists at The Institute of Cancer Research, London, believe their research will open the door to new types of cancer treatment that can control tankyrase more precisely than is currently possible, with fewer side effects. 

The fundamental discovery could have implications for treating various cancers, as well as diabetes and inflammatory, cardiac and neurodegenerative diseases. 

Understanding tankyrase

Tankyrase is an important protein that supports ‘Wnt signalling’ – signals that are essential for the body to maintain stem cells and carry out processes like cell division and development but, when uncontrolled, can fuel bowel cancer, among others. Tankyrase also controls other cell functions critical to cancer, such as the maintenance of the ends of chromosomes, the telomeres. 

To really understand how tankyrase inhibitors work and how to develop less toxic treatments, scientists at the ICR set out to discover new structural information using cutting-edge cryo-electron microscopy.  

The approach allowed them to visualise and capture how tankyrase ‘self-assembles’ into fibres – chain-like structures – and why fibre formation is needed for tankyrase to activate itself. 

Researchers believe the ‘domains’ – specific regions of the protein associating with different functions – that allow tankyrase to assemble and disassemble into different structures are exciting targets for future cancer drugs. 

Better, less toxic drugs

The hope is that researchers will be able to design structurally different tankyrase inhibitors – ones that are safer and more effective, which are urgently needed for treating bowel cancer and other diseases with which tankyrase has been linked. 

Study leader Professor Sebastian Guettler, Deputy Head of the Division of Structural Biology at The Institute of Cancer Research, London, said: “We’re playing catch up – we have all these drugs to block tankyrase being created, but we don’t have enough basic understanding to use them as treatments. 

“We have shown how tankyrase is switched on and can go from a ‘lazy’ enzyme to an active one. If we can create better, less toxic drugs to control this process, we could pave the way for an effective bowel cancer treatment in the future.”

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