New ‘stealth’ drugs give hope in fight on cancer

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Powerful “stealth” anti-cancer drugs able to “sneak” into tumours and destroy them have been developed by scientists.

The drugs can target cancerous areas without causing damage to the surrounding healthy cells, the scientists said.

It is hoped the research, funded by Cancer Research UK, could lead to improved treatment and survival for cancer patients in the future. The study, published today in the Journal of Medicinal Chemistry, showed that the drugs substantially delayed tumour growth in experiments on human breast cancer cells and in animal tests.

The therapy involves deploying a “scout” enzyme to a tumour to mark it for destruction.

The enzyme infiltrates only cancerous cells and lays dormant until non-toxic drugs - called prodrugs - are also sent in.

These drugs are only activated when they react with the “scout” enzyme in the cancerous cell - turning them into a potent cancer-killing drug.

Professor Caroline Springer and her team investigated how these drugs would work with a delivery method called gene-directed enzyme prodrug therapy (GDEPT).

In standard cancer treatment, like chemotherapy, drugs attack anywhere in the body, meaning healthy cells as well as cancerous ones are damaged.

This leads to side effects including hair loss, nausea and fatigue.

But using GDEPT, normal cells should not be affected and this could mean fewer side effects.

In the past, prodrugs of this type have not been powerful enough to reach the enzyme which is sent to the affected cells.

But, in the new study, scientists were able to get the prodrugs to cross through the cell’s membrane and into the cell more efficiently.

Eight prodrugs were tested on three variants of human Breast cancer. Six were found to be effective in targeting the affected cell lines and three were particularly effective in delaying tumour cell growth.

The six positive compounds were then used in animal tests, with two leading to substantial delay in tumour development and two curing the tumours.

Professor Springer, of the Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, said: “We think these drugs are a very promising way forward for cancer treatment.

“They allow you to deliver a drug at a high concentration, which you wouldn’t normally be able to do, as it is too toxic for the rest of the body.

“Although this treatment is more complex than many types of therapies, the fact that it can be so selective in treating cancer means that it is worth exploring further.

“At least one of the eight drugs we developed has been identified as a good candidate for testing GDEPT in clinical trials.”

Professor John Toy, Medical Director at Cancer Research UK, added: “Prodrugs potentially offer a localised treatment for cancer that allows drugs to be targeted specifically to tumours.

“This type of therapy should theoretically work and is showing promise.

He added: “The real test will come when the prodrugs go to clinical trials.”

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