University of Birmingham and Nonacus partner to develop urine test for bladder cancer
The University of Birmingham and Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, have partnered to develop a non-invasive test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.
Bladder cancer is the seventh most common cancer in the developed world1. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria). The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder. Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.
Dr Bryan, Director of the Bladder Cancer Research Centre, commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”
While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results. However, researchers at the University started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of fetal DNA in maternal blood samples. Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.
The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs). Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients. This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours. The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling2.
As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments2. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.
Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis. The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.
Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.
Chris Sale, CEO of Nonacus Ltd, commented: “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”
Tony Hickson, Chief Business Officer at Cancer Research UK, said: "As funders of much of the world-class, cutting-edge cancer research happening in the UK, we offer unique opportunities to commercial partners looking for early involvement in new discoveries. Having Nonacus on board to help transform promising findings in the lab into a new non-invasive test to diagnosis bladder cancer is a testament to how commercial collaborations have the potential to transform the lives of patients. We are looking forward to seeing the next steps as the test is developed and rolled out to the UK and beyond.”
Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said: “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis. A urine test that can rapidly determine who needs these tests will be a very welcome development. Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects. This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer."
- Antoni, S. et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017; 71: 96–108.
- Bryan RT et al. Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23 gene panel with utility for non-invasive diagnosis and risk stratification. BJU Int 2019: 124; 532-544.
About the University of Birmingham
The University of Birmingham is ranked amongst the world’s top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.
Nonacus is focused on delivering innovative technologies to the genomic healthcare sector through the use of cell free circulating DNA as a non-invasive diagnostic tool. Nonacus was created by a team of highly motivated scientists and sector professionals with experience in translating research into routine diagnostic tools that benefit patients. Nonacus provides end to end validated solutions for the use of cell free DNA in genetic testing. More information on the bladder cancer panel of biomarkers is available at https://nonacus.com/bladder-cancer-panel/.
About Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every donation made.
- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
- Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook.
About Action Bladder Cancer UK
- Bladder cancer is not a rare cancer – it is one of the ten most common cancers in the UK - over 20,500 people are diagnosed each year in the UK
- There is a very limited public awareness of bladder cancer, it is a relatively low public health priority and receives little research investment
- ABC UK is dedicated to changing this by:
- working to raise awareness of bladder cancer
- providing much needed support to patients and their families
- encouraging and funding research into bladder cancer
- Action Bladder Cancer UK receives no government funding for its vital work. Every donation makes a difference.
- ABC UK works to get bladder cancer recognised as a common cancer and the level of acknowledgement, public awareness, new treatments and medical research investment which it merits and which those with bladder cancer deserve.
- We want bladder cancer patients to have a voice.
For further information about Action Bladder Cancer UK’s work or to find out how to support the charity, please call 0800 302 0085 or visit www.actionbladdercanceruk.org. Follow us on Twitter and Facebook.