The exciting truth about biomarkers

Prostate cancer biomarkers are big news at the moment.

There was a story in The Telegraph recently that claimed a new diagnostic test had been tested on 77,000 men. The story makes it sound like this test is far closer to being in routine clinical use than it really is. To be fair, it does say that it needs to be approved by regulators before being adopted on the NHS. It just doesn’t mention that it also needs to go through clinical trials.

In reality, this test has been trialled on around 1,000 men so far (I asked one of the scientists named in the article) and it’s only just entering a larger clinical trial. So, the moral of this story is, as ever, don’t believe everything you read in the papers. But that’s not to say that this isn’t a hugely important area of research. It really is.

Knowing what to look out for between men at high risk and low risk of prostate cancer, between aggressive prostate cancers and non-aggressive prostate cancers, cancers that are responding to treatment and cancers that aren’t responding, will make an enormous difference to men with, or at risk of, prostate cancer over the next few years.

And as usual, our researchers are at the cutting edge of this exploding area of prostate cancer research. Here’s a snapshot of some of the research we’re funding into prostate cancer biomarkers.

Determining risk and diagnosis

Professor Ros Eeles, at the Institute of Cancer Research (ICR), is a world-expert in prostate cancer genetics. Her team has played a leading role in identifying many of the genetic risk markers for prostate cancer. She’s now leading a clinical trial called PROFILE, which aims to see whether genetic testing for known markers can identify men at high risk of developing prostate cancer, who can then be closely monitored. Professor Eeles is carrying out some of this work as part of our London Movember Centre of Excellence.

We’re also funding research in Dr Hayley Whitaker’s lab to see whether we can use a panel of the best described blood or urine based biomarkers to not only refine who needs a biopsy, but who would most benefit from an mpMRI scan before biopsy. Not only would this help rule out men with non-aggressive cancers, but also reduce the number of mpMRI scans and biopsies, making pre-biopsy MRI more cost effective for our cash-strapped health services.

Dr Whitaker is working with Professor Mark Emberton, who pioneered pre-biopsy multiparametric MRI at University College London. Combining their expertise means that Dr Whitaker will have access to samples from Professor Emberton’s MRI-guided biopsies, so she can relate them back her biomarker panel ‘scores’ and really make sure they’re accurately predicting how likely someone is to have an aggressive form of prostate cancer.

Choosing the right treatment option

Once a man’s been diagnosed with prostate cancer, his next big decision comes in the form of what treatment – if any – to choose. As we learn more about each man’s individual cancer and what drives its growth, we think that biomarkers can help us work out which men are likely to respond best to which treatment. This would take a huge burden off both men and doctors.

One such marker is PTEN. This is a type of gene called a tumour suppressor. It works by putting the brakes on cell division and growth, so helping prevent cells becoming cancerous. It may be useful in working out who is less likely to respond well to radiotherapy, since prostate cancer cells without a working PTEN gene are more resistant to this type of treatment. Professors Kevin Prise and Richard Kennedy are two of the scientists we’re funding with support from the Movember Foundation as part of the Belfast-Manchester Movember Centre of Excellence. They’re investigating ways to improve response to radiotherapy treatment for men without working PTEN genes, for example by giving another treatment alongside it.

Other researchers at the ICR in London, who are supported in large part by Prostate Cancer UK and the Movember Foundation, have found that treating men who have advanced prostate cancer with a drug called olaparib had astonishing effects. And it was the men with mutations in their genes for repairing DNA, like BRCA1 and BRCA2, who benefited the most. The team is now doing a clinical trial where they test men for this mutation before starting treatment, so that they only recruit the men most likely to benefit into the trial.

This is important because men with advanced prostate cancer don’t have time to waste continuing to take treatments that may have unpleasant side effects yet aren’t actually controlling their cancer, and sometimes it can take a while to notice that it’s not having the effect they were hoping for. That’s where biomarkers to monitor response might be able to help, and this is a big area of current research.

Judging treatment efficacy with liquid biopsies

An increasingly popular method of immediately assessing whether a treatment is still working is using a ‘liquid biopsy’. This is the term for a blood test that measures tumour material – either cells or just DNA – circulating in the blood.

Scientists and clinicians at the ICR are about to start a clinical trial, as part of the London Movember Centre of Excellence work, to investigate whether counting the number of tumour cells in the blood can tell them how well the treatment is working. They will measure the number of circulating tumour cells (CTCs) in the blood at the start of treatment and at various times as treatment progresses. As long as the numbers fall, it suggests that the treatment is working. But as soon as the number of CTCs starts to rise again, it suggests it’s time to switch to another method of controlling the cancer.

Another example of this kind of work also comes from the ICR. Dr Gerhardt Attard is sequencing DNA from a man’s prostate cancer that circulates in the blood to look for mutations in the androgen receptor (a protein that drives prostate cancer growth in its active form). These mutations can indicate when treatments like abiraterone stop working much sooner than waiting for symptoms that the cancer is growing. This may then give doctors and men more time to try alternative treatments.

Real hope for the future

We know that the more we learn about the nuts and bolts of prostate cancer’s molecular biology, the more complicated it gets. But as all of the work we’re funding goes to show, this isn’t necessarily a bad thing. Because the more we understand about the underlying molecular biology of prostate cancer, the more power we have to turn that complexity to our advantage and develop very precise tools to combat cancer in each and every situation. Just look at how far we’ve come in the last few years, and imagine what we can do with another ten.