Researchers at the Cancer Research UK Edinburgh Centre at the University of Edinburgh and the Cancer Research UK Beatson Institute in Glasgow have turned minute fragments of the rare metal palladium into miniature chemotherapy-making ‘factories’ and shown that these can kill prostate cancer cells in the lab.
The scientists say the approach could improve treatment for some prostate cancer patients by providing a way to treat the disease locally with reduced side effects.
The study was funded by Cancer Research UK and the Engineering and Physical Sciences Research Council (EPSRC).
Each year, around 3,300 men in Scotland are diagnosed with prostate cancer and around 930 men in Scotland die each year from the disease. It is the most common cancer in men in Scotland.
Now researchers from Edinburgh and Glasgow are investigating palladium to develop a new way to treat prostate cancer.
Palladium is a safe chemical element which has the ability to catalyse – or activate – certain chemical reactions.
The researchers modified a type of chemotherapy called doxorubicin with a chemical ‘mask’ that keeps it in an inactive form – called a ‘prodrug’ – until it comes in contact with palladium. In zebrafish, they demonstrated that the ‘prodrug’ did not cause toxicity to the heart, a common side effect of the drug that limits its use.
The team then showed that tiny fragments of palladium could switch on the modified drug into the active form of doxorubicin, which successfully killed prostate cancer cells in dishes.
The scientists implanted the palladium devices into prostate tumours in mice, using ultrasound imaging to guide the needle. This showed that the implants were safe and remained at the site of the tumour.
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When the tumours were later removed from the mice and analysed further, the scientists found that the palladium devices maintained the ability to activate the prodrug and trigger cancer cell death – highlighting the possibility that the approach could work for an extended period of time.
Lead scientist Professor Asier Unciti-Broceta, from the Cancer Research UK Edinburgh Centre, said: “We are very excited about this development. There’s more work to do before we can use this in patients, but the results of this study are an encouraging first step. Our hope is that one day a device like this could be implanted in humans to deliver chemotherapy directly into tumours and reduce harmful side effects to the rest of the body.”
The scientists say that because the technology could allow doctors to deliver anti-cancer drugs locally into a tumour, it could reduce the need for surgery to remove the prostate in some patients by enabling their cancer to be treated more precisely.
Based on the extent of a patient’s cancer, treatment for prostate cancer can involve surgery, radiotherapy or cancer drugs – all of which can have difficult side effects. In particular, radical surgery can leave men with problems such as urinary incontinence and difficulty having an erection.
Professor Hing Leung, from the Cancer Research UK Beatson Institute in Glasgow, explained: “For some patients found to have early stage cancer – that is cancer fully within the prostate gland – they may elect to defer treatment but have regular tests to check on their cancer. If there was any suggestion that their cancer is growing they can then consider treatment, surgery or radiotherapy. This avoids over-treatment.
“This group of patients may benefit from having additional treatment through this palladium approach. If proven in people, this new technology could treat prostate cancer locally before it progresses, by delivering anti-cancer drugs directly into the tumour so that the cancer cells could be killed earlier.”
Professor Unciti-Broceta added: “The palladium technology could provide a cost-effective alternative to current treatments, as our study shows it can be implanted into a tumour as a simple injection using ultrasound imaging. And because palladium is a catalyst, it is not used up after releasing the anti-cancer drug within the tumour, so it could be used to deliver multiple treatments.”
The next steps for the scientists will be to test the technology further in mice before seeing if it is safe to use in humans. They also plan to investigate whether it might work in other tumour types such as pancreatic cancer and brain tumour models.
Keith Roxburgh, aged 59, from Edinburgh, was diagnosed with prostate cancer in 2012.
He said: “I was on holiday in Menorca when I first noticed something was wrong. I was having much more of an urge to go to the loo. But I delayed going to the doctor. In my heart I knew something was wrong, so I wasn’t shocked to find out I had prostate cancer. Further tests showed it had spread to my spine and bones.”
The retired IT consultant knows the value of research after taking part in clinical trial. On the STAMPEDE trial, which is supported by Cancer Research UK, he was given a drug alongside hormone treatment to slow down bone thinning. He also had chemotherapy and 19 sessions of radiotherapy.
His cancer is now stable and managed with hormone treatment.
Welcoming the new study, he said: “It’s been fantastic to hear about this new technology that has been developed by scientists in Edinburgh and Glasgow to help people with prostate cancer.
“Without research, we won’t get control over this horrible disease. Going through the treatment was really tough, so it’s exciting to hear that this work might lead to better treatment for prostate cancer in the future with less side effects.”
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Dr Justine Alford from Cancer Research UK said: “Chemotherapy drugs can be very effective cancer treatments, but their side effects can not only lower patients’ quality of life but also limit their usefulness. This innovative early research showcases a creative way to solve this problem that, if proven, could not only make anti-cancer drugs more effective by targeting them right at the tumour, but kinder too.
“We look forward to the next stages of this research, where hopefully the potential of this promising approach will be demonstrated further.”