Prostate cancer is finally catching up with similar diseases in having treatments that can target an individual’s specific cancer – and it’s thanks to the game-changing research that you help us fund. Dr Ian Le Guillou meets a man who is already benefitting from this new ‘precision medicine’ approach, and explains how it all works thanks to our brilliant researchers.

14 Aug 2017

Twelve years after first being diagnosed with prostate cancer, Douglas Baker was starting to feel desperate. “The doctor said there wasn’t anything left that he could offer me,” he says.

Douglas had been through rounds and rounds of treatment, but in the end the cancer had spread to his lymph nodes and his liver. The cancer had become resistant to all available drugs and he’d run out of options.

“I’ve tried to never worry about my condition and just get on with life, but that was one of my low points,” he says. “I was in hospital four times in five months.”

That was when his doctor suggested taking part in a clinical trial to test a new treatment. “I was told that it was a drug for ladies with ovarian cancer, so I was a bit surprised that they were giving it to me,” says Douglas.

The trial is led by researchers at The Institute of Cancer Research (ICR), who are testing a drug known as olaparib to see if it could work in certain men with prostate cancer.

Targeting men with missing ‘table legs’

Ovarian cancer and prostate cancer might seem poles apart at first glance. But when you look beneath the surface, similarities start to appear. All cancers come from changes to DNA that cause cells to grow out of control.

“As we’ve learnt more about these genetic changes, it’s clear that ‘prostate cancer’ is not a good enough description,” says Dr Iain Frame, director of research at Prostate Cancer UK. “We need to know exactly what changes are driving each man’s cancer to get the best treatment for him.”

Olaparib is a type of drug known as a PARP inhibitor, which works by stopping one method that cells use to repair breakages in DNA. If a cancer cell is already struggling to repair DNA damage, then olaparib could be enough to kill it.

“It’s a bit like a table with a leg missing,” says Dr Joaquin Mateo from the ICR. “With just three legs, the table will stay standing – even if it’s a bit unstable. If we take out another leg, the table collapses.”

Dr Mateo is being funded by Prostate Cancer UK to find out which men might benefit from being given olaparib –which men already have one ‘table leg’ missing.

“They told me that not everyone is suitable for this drug,” says Douglas. Before the trial, he had a biopsy of his lymph nodes and had several blood tests. “I couldn’t believe how many tests they were doing. They were taking lots of samples and putting them on ice.”

The samples and test results from men like Douglas are helping Dr Mateo to find biomarkers, or chemicals in the body, that doctors can test for to see if olaparib will work for them. In Douglas’ case, the tests indicated he was suitable and the results of the drug have been clear.

“This trial has really turned me around, it really has,” he says. “I went on holiday to Spain last year, which I didn’t think I’d be able to manage again but I did. I’ve been very, very lucky – even if that seems like a funny word to use.”

Getting precise to fulfil our treatment ambition

This ‘precision medicine’ approach – using a test to select the best treatment – has worked successfully in other cancers, too. The breast cancer drug, Herceptin, blocks the activity of a protein known as HER2, which is only present in one-in-five cases of breast cancer.

For those women who are ‘HER2 positive’, the drug works well and can even help to reduce the chances of the cancer coming back after surgery. But if Herceptin was given to a woman who was ‘HER2 negative’, then it wouldn’t help her at all. So, a clinical trial of Herceptin for all women with breast cancer would look like a failure.

This is why precision medicine is so promising, as it could offer a huge range of treatments that target specific cancers. And since one of Prostate Cancer UK’s key priorities is to reach the point where each man can get the best treatment for his individual cancer, identifying precision medicines will play a big part in achieving this.

“In 2015, we set out a challenge to scientists, gathering a dozen of the best minds in this area, to design a number of large-scale clinical trials that could make our vision a reality,” says Dr Frame. “Unfortunately, they concluded that there hasn’t yet been enough research to understand how potential treatments work and which men would benefit.

“So, we launched a funding call, offering over £1 million for a research project to gather the evidence and understanding needed to get several treatments ready for major clinical trials.”

This project will contain several separate but linked studies designed to help us find new, targeted treatments for men with advanced prostate cancer who are still receiving hormone therapy.

There traditionally hasn’t been as much research into these men, as it’s more difficult to find new treatments at this stage. However, it has the potential to help many more men and have greater impact.

Focusing on genetics and what drives the cancer

The treatments are only half of the equation: we also need to know which men are going to benefit. To do this, we need simple, reliable tests to understand what is driving the cancer.

In May, research funded by Prostate Cancer UK developed a blood test to detect DNA released by the cancer, which could potentially identify men with advanced prostate cancer who will not respond to the standard treatments, abiraterone and enzalutamide.

This test is now going to be confirmed in a trial, also funded by us. If it is successful, it could be used to select men’s treatments and potentially become the first precision medicine approach for prostate cancer.

This new test shows that matching genetics to the treatment not only works for new drugs, but also makes the most of what we already have. This relies on a better understanding of which genes are important, precisely how existing treatments work in the body, and when new mutations arise.

Some tests, like the abiraterone blood test mentioned, focus on new genetic mutations that happen as the cancer evolves in response to treatment. However, in the future we might be able to find specific treatments for men with mutations that they have inherited from their parents. Prostate cancer is influenced by genetics, and if a man has a brother or father with prostate cancer then he has a two-and-a-half times greater risk of having the disease himself.

In some cases, families might carry mutations in the BRCA genes, which are most commonly associated with breast cancer but also raise the risk of prostate cancer. Our previous research has suggested that these men might benefit more from surgery than radiotherapy. While this isn’t confirmed, it does highlight how a better understanding of what is driving the cancer can help doctors to treat it more effectively.

For Douglas, the benefits of more targeted treatment are already obvious. Scans show that the tumours in his lymph nodes and liver are shrinking in response to olaparib. However, he’s aware that there’s no way of knowing how long it will continue to work for him.

“Whatever happens with me, I just hope and pray that it helps someone else further down the line,” says Douglas. “That’s my main aim.”

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