Developing a non-invasive assay for the detection of prostate cancer

Dr Feber and his team aim to improve the way that prostate cancer is diagnosed. They’ve developed a test that looks at prostate cancer specific DNA changes that can be detected in the blood of men with prostate cancer. In this project they want to compare their new liquid biopsy based test to the current standard diagnostic pathway (PSA test and TRUS biopsy). This will first make sure that their new test really can tell the difference between men who have cancer and men who don’t, and secondly check whether it’s better than PSA/biopsy at ruling out men who don’t have cancer and detecting men with aggressive forms of prostate cancer who should go on to be treated. If so, 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; that is, changes in the DNA code itself, but rather for changes in the way the DNA looks, and how it works, after it becomes cancerous. You can think of this 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 – a light-weight fuel-cell, a roll-cage, proper racing seats, heavy duty restraints instead of seatbelts, and metal skid plates on the undercarriage for example. 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, 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 lung, kidney, bladder or anywhere else, and whether it’s normal DNA or cancer DNA. They also think that some of these changes can tell them how aggressive the cancer is.

Dr Feber and his team have identified a panel of prostate cancer specific DNA modifications that can be detected in tumour DNA circulating in the blood. The team thinks that this panel could also be useful in monitoring how well men are doing after a first-line prostate cancer treatment, and keeping track of whether or when the cancer comes back. They’ll test this by taking blood samples from men with prostate cancer before and immediately after treatment, as well as at intervals during their two year post-treatment follow up. They will see whether their new epigenetic test gives a timelier, cheaper and more precise indication of when and where the cancer has returned/spread to than monitoring a patient by PSA tests and imaging.

The team hopes that the data they gather during this award will lead to funding for a follow-on clinical trial to confirm the benefits in using their assay for prostate cancer diagnosis and post-treatment monitoring, by which point, they aim to have all the regulatory ‘i’s dotted and ‘t’s crossed to be able to make this routinely available to patients.

Grant information

Reference - MA-TR15-009
Researcher - Dr Andrew Feber
Institution - University College London
Award - £333,951.00