Bowel cancer treatment breakthrough

Posted on the 5th December 2022

A key protein could pave the way for less toxic drugs being used to treat bowel cancer.

The elusive but important tankyrase protein plays a particularly important role in helping drive bowel cancer and is involved in a wide range of processes in cells.

Scientists at The Institute of Cancer Research, London (ICR) used Nobel Prize-winning techniques to discover how the protein switches itself on and off by self-assembling into 3D chain-like structures. In doing so, the team have been able to control tankyrase more precisely than is currently possible, with fewer side effects.

The scientists believe their findings could also have implications for future treatment of other cancers, as well as diabetes and inflammatory, cardiac and neurodegenerative diseases.

In the last 10 years, scientists have developed drugs to block tankyrase to treat bowel cancer – but because of the complexity of the processes involved, the drugs had too many side effects to reach clinical trials.

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

This extremely powerful type of microscopy freezes samples at -180°C, enabling minute details of protein shape to be imaged.

This allowed them to visualize and capture how tankyrase ‘self-assembles’ into fibers – chain-like structures – and why fiber formation is needed for tankyrase to activate itself.

Researchers believe specific regions of the protein that allow it to assemble and disassemble into different structures are exciting targets for future cancer drugs.

The hope is that they will be able to design structurally different tankyrase inhibitors – safer and more effective ones 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 ICR, said: “Our study has provided vital new information about a particular protein molecule called tankyrase, which plays an important role in bowel cancer and other diseases but has so far eluded our understanding.”