Scientists Make Major Cancer Breakthrough By Killing 'Undruggable' Proteins

With the 'kiss of death'.

Scientists have made a cancer breakthrough after learning how to kill “undruggable” proteins using a technique they have nicknamed the “kiss of death”.

For a long time, researchers have known about the vital role that proteins play in spreading cancerous tumours around the human body, but were unable to halt them in their tracks.

Professor Alessio Ciulli explained: “We know of many proteins which are active in causing diseases, but which we have been unable to block from going rogue or to stop them when they do.”


Now the team at the University of Dundee has found a way to neutralise these stubborn proteins, Ras and Myc, which had previously been deemed untouchable by drugs.

The process works by introducing small molecules to target these bad proteins, that then bind to them, neutralise them and start a chain of events that degrades them and breaks them down in the body.

However, in the past, the major stumbling block has been finding the molecules that would work to bind and at the same time hamper functionality. As proteins can often fool regulators within the cell and can be difficult to pin down.

So instead of using these small molecules to locate and disable the protein, the new study, is working on a way to attract the neutralising proteins, which then bind to the bad neighbour and act against it.

Ciulli said: “Crucially, we have also found that it is not enough for this neutralising protein to sit close to the bad protein, it has to make direct contact with it, to `kiss’ it. And not just a little peck, but a real `Gone With The Wind’ embrace. We call this a ‘kiss of death’, as it is the key to ensure the degradation of the bad protein.”

The work focused on pairing one of the BET bromodomain proteins, BRD4, which is an attractive drug target for cancer, with a selective BRD4 degrader called MZ1.

“The road to turning degraders into drugs will be long and winding and we cannot get there on our own. It is exciting to see signs of serious commitment from the pharmaceutical industry,” said Ciulli.


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