Two research projects, using cutting-edge liquid biopsy technology to help improve diagnosis and treatment of men with prostate cancer, have been awarded funds by Prostate Cancer UK with the hope they'll be used with real patients in the near future.
Today, we’re announcing two new Translational Research Awards, thanks to funds from The Movember Foundation. These grants aim to take game-changing science from the lab and into the clinic to be used with real patients by the time they finish. Both projects focus on liquid biopsies – one of the hottest topics in prostate cancer research at the moment. But each concentrates on a different end of the care spectrum.
Dr Gerhardt Attard from the Institute of Cancer research in London is focused on improving treatments for advanced disease, while Dr Andrew Feber, from University College London is concentrating on improving prostate cancer diagnosis. You can read more about the way that liquid biopsies look set to transform prostate cancer care in our blog, but here's more about what each of the projects will be doing...
Dr Attard, from the Institute of Cancer Research and the Royal Marsden Hospital, will run a clinical trial called PARADIGM. The overall aim of this trial is to determine whether doctors and clinicians can use a simple blood test to determine the treatment that’s most likely to work for a man with advanced, hormone-resistant prostate cancer.
Once they’ve decided to join the trial, men will have a blood test. Then Dr Attard and his team will extract the tumour DNA from the blood and test it for changes in the gene that instructs the Androgen Receptor.
In a previous project funded by Prostate Cancer UK and The Movember Foundation, Dr Attard showed that men whose prostate cancers had particular changes in the Androgen Receptor gene were likely to be resistant to treatments like abiraterone and enzalutamide. This genetic change could be detected in the tumour DNA from the blood long before the man started feeling symptoms of his cancer worsening.
Although men with these gene mutations may be resistant to abiraterone or enzalutamide, they might respond better than expected to docetaxel or cabazitaxel chemotherapy
In the PARADIGM trial, Dr Attard will follow up on this work and other data suggesting that, although men with these Androgen Receptor gene mutations may be resistant to abiraterone or enzalutamide, they might in fact respond better than expected to docetaxel or cabazitaxel chemotherapy.
Dr Attard and his team will now use his liquid biopsy test for Androgen Receptor mutations on men who haven’t already started treatment. This trial will first seek to confirm that second-line hormone therapies don’t work well for men with changes to the Androgen Receptor gene. It will also determine if these same men will actually do much better on chemotherapy instead.
Overall, the PARADIGM trial should clearly demonstrate whether testing men for changes to the Androgen Receptor gene as soon as their cancer becomes hormone resistant, then offering them treatment based on the result of that test, would mean that men get access to the medication most likely to work for them the first time around.
Dr Feber and his team aim to improve the way that prostate cancer is diagnosed and monitored. They’ve developed a test that looks at prostate cancer-specific DNA modifications that can be detected in the blood of men with the disease.
In this project, they want to compare their new liquid biopsy-based test to the standard way of diagnosing prostate cancer (a PSA test and TRUS biopsy). They’ll work out whether this could be a quicker, cheaper, less invasive and more accurate way to diagnose aggressive forms of prostate cancer than we have at the moment.
What’s interesting about this test is that it doesn’t look for mutations in the DNA's code itself. Rather, it looks for changes in the way the DNA appears and how it works after it becomes cancerous. Think of it like trying to pick out a rally car from a line up of normal road cars. The actual structure of the car and its engine is basically the same, but the rally car has important differences that make it stand out, like a roll-cage and racing seats.
This sort of technology could be a cheaper way of monitoring how well men are doing after prostate cancer treatment than the current testing, telling a doctor sooner and more accurately when a cancer has returned
It’s a similar situation for DNA molecules. As they become cancerous, the DNA molecules themselves gain additional 'bolt on' chemical structures that change the way they look and work, while leaving the basic code the same. These are known as epigenetic changes, and they can be extremely revealing.
Just like a car aficionado might be able to look at an engine and tell you exactly who made it and what model it came from, so the pattern of epigenetic changes to the DNA can tell scientists whether that DNA is from the prostate rather than anywhere else, and whether it’s normal or cancer DNA. They also think that some of these changes can tell them how aggressive the cancer is. This sort of technology could also be a cheaper way of monitoring how well men are doing after a first-line prostate cancer treatment than the current testing, telling a doctor sooner and more accurately when a cancer has returned.
As well its DNA, looking at the cells a cancer sheds into the bloodstream is another way that liquid biopsies could change treatment for men with prostate cancer. We’ve talked about ways that some of our funded researchers are using this information before. For example, in the CTC-STOP trial in the London Movember Centre of Excellence and the ADRRAD trial in the Belfast-Manchester Movember Centre of Excellence, they've shown that Circulating Tumour Cells (or CTCs) in the blood can be used to tell when a man’s treatment just isn’t working for him, which could be really important in saving him precious time.