Scientists have developed a three-in-one blood test that has the potential to transform the treatment of advanced prostate cancer through the use of precision drugs designed to target mutations in the BRCA genes.

Through testing cancer DNA in the bloodstream, researchers found they could pick out which men with advanced prostate cancer were likely to benefit from treatment with new drugs called PARP inhibitors, writes The Institute of Cancer Research (ICR).

The researchers at the Institute, London and The Royal Marsden NHS Foundation Trust proclaim that their test is the first to be delivered for a precision prostate cancer therapy targeted at specific genetic faults within tumours.

Additionally, the test analysed the DNA in blood after the treatment had started so people who were not responding could be identified and switched to alternative therapy in as little as four to eight weeks. They also used the test to monitor a patient’s blood throughout the treatment, quickly picking up signs that the cancer was evolving genetically and might be becoming resistant to the drugs.

The tests could eventually allow the PARP inhibitor olaparib to become a standard treatment for advanced prostate cancer in the future. It will do this by targeting the drug at the men most likely to benefit, picking up early signs that it might be working, and monitoring for the later development of resistance.

The study has been published in the Cancer Discovery journal, and it is thought it could help to extend or save lives, by targeting treatment more effectively, while also reducing the side-effects of treatment and ensuring patient don’t receive drugs that are unlikely to do them any good.

It is the first test that can identify which genetic mutations prostate cancers use to resist treatments with olaparib, and has the potential to be adapted to monitor treatment with PARP inhibitors for other cancers. Researchers at the ICR and The Royal Marsden collected blood samples from 49 men at The Royal Marsen with advanced prostate cancer enrolled in the TOPARP-A phase II clinical trial of olaparib.

Olaparib is efficient at killing cancer cells that have errors in genes that have a role in repairing damaged DNA such as BRCA1 or BRCA2. Some patients respond to the drug for years, but in other patients, the treatment either fails early, or the cancer evolves resistance.

When looking at the levels of cancer DNA circulating in the blood, the researchers found that patients who responded to the drug had a median drop in the levels of circulating DNA of 49.6% after only eight weeks of treatment, whereas cancer DNA levels rose by a median of 2.1% in patients who did not respond.

Men whose blood levels of DNA had decreased at eight weeks after treatment survived an average of 17 months, compared with only 10.1 months for men whose cancer DNA levels remained high. The researchers performed a detailed examination of the genetic changes that occurred in cancer DNA from patients who had stopped responding to olaparib. They discovered that cancer cells had acquired new genetic changes that cancelled out the original errors in DNA repair – particularly in the genes BRCA2 and PALB2, which had made the cancer susceptible to olaparib in the first place.

The research puts into action the central aim of the ICR’s and The Royal Marsden’s research strategy, which is to overcome cancer’s adaptability evolution and drug resistance.

Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, commented, “Our study identifies, for the first time, genetic changes that allow prostate cancer cells to become resistant to the precision medicine olaparib.

“From these findings, we were able to develop a powerful, three-in-one test that could in future be used to help doctors select treatment, check whether it is working and monitor the cancer in the longer term. We think it could be used to make clinical decisions about whether a PARP inhibitor is working within as little as four to eight weeks of starting therapy.

“Not only could the test have a major impact on treatment of prostate cancer, but it could also be adapted to open up the possibility of precision medicine to patients with other types of cancer as well.”

Professor David Cunningham, Director of Clinical Research at The Royal Marsden NHS Foundation Trust, explained, “This is another important example where liquid biopsies – a simple blood test as opposed to an invasive tissue biopsy – can be used to direct and improve the treatment of patients with cancer.

Dr Matthew Hobbs, Deputy Director of Research at prostate Cancer UK, added, “To greatly improve the survival chances of the 47,000 men diagnosed with prostate cancer each year, it’s clear that we need to move away from the current one-size-fits-all approach to much more targeted treatment methods. The results from this study and others like it are crucial as they give an important understanding of the factors that drive certain prostate cancers, or make them vulnerable to specific treatments.

“However, there is still much more to understand before the potentially huge benefits of widespread precision treatment for prostate cancer will reach men in clinics across the UK. That is why Prostate Cancer UK is investing so heavily in this area, including supporting this research released today.”