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Dundee scientists discover how to destroy ‘undruggable’ cancer-causing protein

Dr Gopal Sapkota.
Dr Gopal Sapkota.

Tayside scientists have discovered how to destroy a cancer-causing protein, and hope the move lead to new treatments within the next decade.

Researchers from Dundee University have found a new way to target K-Ras, a protein mutation known to cause cancers including lung, bowel and pancreatic.

The School of Life Sciences team, led by Dr Gopal Sapkota have shown how they can degrade the protein using a “protein missile” they have engineered, called AdPROM.

Dr Sapkota said: “K-Ras is the Holy Grail of cancer targets, so the knowledge that it can be targeted for degradation is an extremely promising discovery.

“This potentially allows for any small molecule that binds K-Ras, rather than just inhibitors which have proven to be elusive, to be converted into a degrader.

“In the next 10 years I would hope we have options available to target those cancers that are caused by K-Ras mutations.

“The idea that we can remove disease-causing proteins from the cell is very exciting, both in terms of research and drug discovery.

“Targeted destruction of disease-causing proteins is an exciting new approach to tackling the so-called undruggable targets, which is something many believed K-Ras to be.”

The AdPROM technology is relatively simple to assemble and can be used in any cell. The system uses small probes, termed nanobodies or monobodies, which bind and recruit specific target proteins to the cells’ own protein degradation machinery.

The findings will be revealed in two papers published in Cell Chemical Biology today [Tuesday].