Targeting hardy cancer cells that survive radiotherapy

The team in Cardiff will test the ability of a new drug developed in their lab to kill prostate cancer stem cells which they believe are responsible for driving cancer spread even after surgery or radiotherapy in men with high-risk localised prostate cancers.

Even when cancer is caught and treated before it spreads outside the prostate it currently comes back far too often. In fact, about one third of men who have a radical prostatectomy or radiotherapy find that their PSA level starts to rise and their cancer returns a few years after their first treatment. A large percentage of deaths from prostate cancer occur in men whose cancer has returned after initial treatment and so finding ways to prevent recurrence will be a cornerstone in our fight to reduce the number of men dying from prostate cancer.

The lead scientist believes that there is a subset of very resilient cancer stem cells in the tumour that are resistant to, or somehow evade, primary treatment. These cells lead the spread of prostate cancer around the body in high-risk men. Their team has developed a novel anti-cancer drug that specifically targets these cancer stem cells, and believes that giving this drug to men at high-risk of their cancer spreading outside the prostate could prevent this recurrence from happening.

Their drug works by blocking a protein called cFLIP that’s produced at very high levels in high risk, localised prostate cancers. cFLIP stops the cancer stem cells from dying when they get damaged, so blocking this protein should re-sensitise these cells to treatment.

Firstly they’re going to test their theory on prostate cancer cells taken straight from the patient and grown in the lab. The advantage of this is that they will have cells from a range of patients with different tumour types to test the drug on. They will test how well the drug works on its own, but also in combination with other treatments.

Then they’ll move to testing the new drug in ‘live’ prostate cancer samples straight from the clinic.

Once all the tests above have confirmed which tumour types are most responsive to their drug, the team will transplant some of these tumours into mice, so that they can not only test the effect of the drug on a whole-body system, but also do some longer studies to start to address the long term consequences of treatment with this drug, and whether it can in fact prevent the cancer starting to spread again after surgery or radiotherapy.

Grant information

Reference - RIA15-ST2-016
Researcher - 
Dr Richard Clarkson
Institution - Cardiff University
Award - £279,632