New research collaboration to transform prostate cancer diagnostics
In November, we held the first of our Diagnostics Growth Hub events, Biomarker Matchmaking.
The event aimed to address the gap between university research and clinical adoption of diagnostic biomarkers by bringing together academics and industry – invited for their potential synergies – to present and network in a closed setting. The goal was to spark research collaborations that would bring more diagnostic biomarkers to the clinic, since currently less than 10% of known biomarkers reach the patient to improve survival or outcomes.
We are now delighted to introduce the first of three research collaborations that resulted from that first event.
Technology platform company Sysmex is collaborating with Professor Yong-Jie Lu, Centre for Cancer Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London. To tell us more about their new partnership to develop prostate cancer diagnostics, we spoke with Professor Lu and Simon Young, Director of Research and Development Centre UK at Sysmex.
Q: Professor Lu, please tell us about your focus on prostate cancer diagnostics and what problem you are trying to solve.
Prostate cancer (PCa) is the most common cancer in men in the industrialised world, with 1 in 6 developing PCa in a lifetime. Approximately 48,000 new cases and 12,000 deaths occur annually in the UK. The current method for early detection is prostate specific antigen (PSA) testing. This is a blood test that allows for early diagnosis, significantly reducing the rate of patients diagnosed with lethal metastatic disease, hence dramatically increasing the survival rates of PCa.
However, the problem is that PSA is prostate specific, not PCa specific. Blood PSA levels can increase in many non-malignant prostate diseases, such as prostatitis. This can mean that more than half of patients who test as having abnormal PSA (>4 ng/mL) do not actually have PCa. The only way to know for certain, is for the patient to undergo a diagnostic prostate tissue biopsy. This is a painful procedure, associated with significant morbidity due to complications such as infections, even sepsis. Additionally, many PCa cases are inactive, or developing so slowly that around half of patients diagnosed with early-stage PCas will not die of the disease if left untreated.
So, the current practice of PSA tests and subsequent biopsy leads to a huge amount of unnecessary biopsies – over 1 million annually in Europe. It also causes over-diagnosis and over-treatment to many men, causing significant harm to patients, and a waste of valuable healthcare resources.
Q: What do you see as the solution?
Our research has been focused on circulating biomarkers for several years. This includes circulating tumour cells (CTCs), plasma exosomes and other circulating cells, with several publications and two patents filed. By using these biomarkers, it’s possible to achieve a more accurate detection of clinically significant PCa.
We have developed a method of CTC analysis in collaboration with ANGLE plc (including CTC positivity and the CTC gene panel). In combination with PSA levels, it predicts biopsy outcome of clinically significant PCa highly accurately, but these methods are time-consuming and require specially trained people to perform. What we need is a simple, low-cost assay to accurately detect clinically significant PCa. This could dramatically change the PCa diagnostic pathway, and even lead to a PCa screen. This is where we think Sysmex’s technology can help.
Q: Simon, can you explain how your platform works?
Sysmex is a diagnostics technology company, and we are largely disease-agnostic. We make large automated chemiluminescent analyzers, typically installed in national health laboratories, or big commercial laboratories, for analysing patient samples for a variety of diseases. They use fairly established technology – using two antibodies to recognise the antigen of the protein you’re looking at. We’ve been making these for many years and so the whole system is optimised, with very low variability, high accuracy and very high sensitivity.
Q: Why were you interested in the Biomarker Matchmaking event?
As developers of diagnostic tests, we need access to clinical samples, because we have to show that the diagnostic works on those real samples, and also generate a lot of biology around that particular biomarker. For example, how does the biomarker vary with age, with gender, with disease severity? What are the confounding problems? How do you handle samples? There are a huge number of questions, which, as assay manufacturers, we have to know the answers to, in part because we have to present those answers to the regulatory authorities.
So, we look to collaborate with researchers who have developed this knowledge, have the samples, and are experts in their field, but it’s a real challenge just finding out where they are and who’s doing what. There are a lot of universities in the UK, a lot of departments and a lot of people doing work in those departments. So just reaching out, and actually finding the right people is the difficult bit. And that’s why I hadn’t met Professor Lu before, until the event organised by MedCity in collaboration with NIHR London In Vitro Diagnostics Cooperation and Dr Christopher Peters at Imperial College. The event brought together researchers who were very well matched for Sysmex, and I thought Professor Lu’s work was very interesting, addressing a big problem, with the right type of sample for our platform.
Q: And what will the collaboration now involve?
During our circulating biomarker study, we have collected and stored more than 1,000 plasma samples from PCa patients and controls, which can be used for this study, and the clinical blood sample collection is ongoing. We have also developed a panel of PCa biomarkers, which are proteins released from CTCs.
Working with Professor Lu’s reference biomarker, combined with a pair of antibodies made against the protein, we will develop assays for the blood biomarkers on our High Sensitivity ChemiLuminescence (HISCL) enzyme immunoassay platform, and then use this to screen sample sets and generate clinical insight into the value of the biomarkers. Then, using those three key reagents – the reference protein, and the two antibodies – we can make a diagnostic kit. We really want to put diagnostic kits like these in the hands of doctors. Doctors will decide their real value, but first we have to provide them.
We think there is a real opportunity here to develop a more effective diagnostic test that will cut down on the problem of over-diagnosis and mortality, by removing the aggressive biopsies that are unnecessary in around half of the patients being diagnosed currently.
About Professor Lu
Prof Yong-Jie Lu is Professor of Molecular Oncology at the Centre for Cancer Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London. He joined QMUL in 2003, after spending eight years as a researcher at The Institute of Cancer Research in Sutton, South London. He studied at Henan Medical University and Harbin Medical University, before completing his PhD in Pathophysiology at the Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing.
Simon Young graduated from Cambridge University with degrees in Electrical Engineering and Veterinary Medicine, and a PhD in horse lung mechanics. He specialised in veterinary anaesthesia and practised at the Animal Health Trust in Newmarket before moving to Canada, where he was an assistant professor in the Ontario Veterinary College at the University of Guelph. He then started a career in the pharmaceutical industry, working first at Merck in the USA and then for AstraZeneca in the UK. In 2020, he joined Sysmex Corporation to head up the Research and Development Centre in Cambridge, which develops new applications for Sysmex diagnostic technology and partners with academic and business groups to develop novel diagnostic biomarkers.
Sysmex Corporation is a world leader in clinical laboratory systemization and solutions, including laboratory diagnostics, laboratory automation and clinical informatics. Serving customers for more than 50 years, Sysmex focuses on technological leadership in diagnostic science and information tools that make a difference in the health of people worldwide. We are a leader in haematology and are expanding our products and services in the haemostasis, immunochemistry and cancer genomics fields. Our Research and Development programs focus on the development of testing and diagnostic technologies that are innovative, original and optimize individual health. We are shaping the future of health care by pioneering next generation technology, from the use of artificial intelligence and big data analysis to developing medical robotics. Sysmex is headquartered in Kobe, Japan, and has subsidiaries in North America, Latin America, Europe, the Middle East, Africa, China and Asia Pacific and employs more than 9,000 people worldwide. Sysmex Corporation is listed in the top tier of the Tokyo Stock Exchange.