Breast precancer cell colony in 3D Dr Gilmore and Simon Saadati
Developing radical new strategies and technologies to detect cancer at its earliest stage is the bold ambition of a new transatlantic research alliance, announced today by Cancer Research UK and partners.
Early detection is essential to help more people beat cancer – a patient’s chance of surviving their disease improves dramatically when cancer is found and treated earlier.
Understanding the biology of early cancers and pre-cancerous states will allow doctors to find accurate ways to spot the disease earlier and where necessary treat it effectively. It could even enable ‘precision prevention’ – where the disease could be stopped from ever occurring in the first place.
UK statistics highlight the major improvements in survival that could be achieved. 5-year survival for six different types of cancer is more than three times higher if the disease is diagnosed at stage one, when the tumour tends to be small and remains localised, compared with survival when diagnosed at stage four, when the cancer tends to be larger and has started to invade surrounding tissue and other organs.*
Advances in early detection technologies will help decrease late-stage diagnosis and increase the proportion of people diagnosed at an early and treatable stage, so a future for more patients can be secured.
Cancer Research UK is setting out a bold ambition to jump-start this under-explored field of research, collaborating with teams of scientists from across the UK and the US.
The International Alliance for Cancer Early Detection (ACED) is a partnership between Cancer Research UK, Canary Center at Stanford University, the University of Cambridge, the OHSU Knight Cancer Institute, UCL and the University of Manchester.
Great strides have been made through existing screening programmes, such as for bowel, breast and cervical cancer, and increasing public awareness and GP urgent referral of patients with suspicious symptoms. However, for many cancer types no screening tools exist and new technologies for detecting cancer have been slow to emerge.
Previously, researchers taking on this challenge have faced many barriers, including lack of funding and collaboration opportunities, meaning research has been small scale and disconnected. Individual research groups have chipped away at big challenges with limited success. By combining the ‘fire power’ of some of the leading research institutions in the world in early detection, ACED will accelerate breakthroughs, leading to quicker benefits for patients.
However, like looking for a needle in a haystack, the very low levels of tell-tale early cancer signs make it incredibly difficult to detect cancer early. Scientists in the Alliance will work together at the forefront of technological innovation to translate research into realistic ways to improve cancer diagnosis, which can be implemented into health systems. Potential areas of research include:
- Developing new improved imaging techniques and robotics, to detect early tumours and pre-cancerous lesions
- Increasing understanding of how the environment surrounding a tumour influences cancer development
- Developing less invasive and simpler detection techniques such as blood, breath and urine tests, which can monitor patients who are at a higher risk of certain cancers
- Searching for early stress signals sent out from tumours or surrounding damaged tissue as a new indication of cancer
- Looking for early signs of cancer in surrounding tissue and fluids to help diagnose hard to reach tumours
- Harnessing the potential of artificial intelligence and big data to look for signs of cancer that are undetectable to humans.
As part of the Cancer Research UK’s early detection strategy, the charity will invest an essential cash injection of up to £40 million over the next five years into ACED. Stanford University and the OHSU Knight Cancer Institute will also significantly invest in the Alliance, taking the total potential contributions to more than £55 million.**
Michelle Mitchell, Cancer Research UK’s chief executive, said: “Now is the time to be ambitious and develop effective new ways to detect cancer earlier. It’s an area of research where we have the potential to completely change the future of cancer treatment, turning it into a manageable and beatable disease for more people.
“Real progress in early detection can’t be achieved by a single organisation. Benefits for patients will only be realised if early cancer detection leaders from around the world come together. No more siloes, no more missed opportunities; let us tackle this problem together and beat cancer.”
The Prime Minister said: “Every two minutes, someone in the UK has their world turned upside down when they are diagnosed with cancer. Thanks to the pioneering work of UK researchers and our world-beating NHS, more people are surviving than ever.
“However, there is more to do to detect and cure this disease earlier. That is why I am pleased to welcome this new UK-US alliance, driven by Cancer Research UK.
“This is the transatlantic partnership at its very best. Our brilliant scientists will be able to work together to develop detection technologies and implement them in our health service, so we can find cancer earlier and ultimately save people’s lives.”
It’s crucial that new early detection advances can also be quickly implemented into the health service to save and transform lives. The Alliance will be a globally unique platform that is able to test and validate early detection innovations in real-world hospital and healthcare settings. The partners will engage with pharmaceutical and biotechnology companies in the research field to ensure discoveries can achieve economies of scale and reach patients as soon as possible.
The Alliance will also be in a unique position to train and develop a new generation of early cancer detection research leaders, learning from the very best that both countries and all five centres have to offer.
The benefits of investing in early detection research are clear. And through ACED, the global early detection research community will grow and develop technological innovations that radically improve outcomes for people diagnosed with cancer.
*Based on 5-year age-standardised net cancer survival in England of adults diagnosed between 2013 and 2017, followed up to 2018; cancer sites for persons: colorectal, kidney, lung. For women specifically: breast, uterine and ovary.
For example: 98% of breast cancer patients survive their disease for five years or more if it’s diagnosed at the earliest stage (stage 1), compared to just 26% of patients when cancer is diagnosed at the latest stage (stage 4). But at the moment only around 44% of breast cancer patients (with a known stage) are diagnosed at the earliest stage.
Diagnosing lung cancer at its earliest stage increases the chance of surviving the disease for 5 years or more to 57%, compared to only 3% when it is diagnosed at the most advanced stage. At the moment, only around 21% of people with lung cancer (with a known stage) are diagnosed at the earliest stage, compared to around 50% who are diagnosed at stage 4, when treatment options are limited.
Source: “Cancer survival in England – adults diagnosed” released by the ONS, August 2019. Incidence by stage in England data source: “Stage breakdown by CCG 2017” released by National Cancer Registration and Analysis Service (NCRAS), February 2019.
**Cancer Research UK will invest up to £40 million in the next five years into the Alliance. Over the next five years Cancer Research UK is set to fund around £3 million per UK Member Centre to support their growth and up to £30 million to support collaborative research and infrastructure across the Alliance. Each US party will contribute up to $10 million to research projects and infrastructure. Taking the US contribution from the two partners to up to $20 million.
Canary Center at Stanford University
The Canary Center at Stanford for Cancer Early Detection brings together more than 40 members from multiple disciplines across Stanford University. It is directed by Professor Sanjiv Sam Gambhir MD, PhD and co-directed by Professor Utkan Demirci, PhD.
The Canary Center at Stanford was founded in 2009 as the first center in the world entirely dedicated to cancer early detection. Its mission is to discover and implement minimally invasive diagnostic and imaging strategies for the detection and prognostication of cancers at early, curable stages.
The Canary Center is the pioneer in integrating research on in vivo diagnostics (e.g., molecular imaging tests) and in vitro diagnostics (e.g., blood tests) to deliver these strategies, by housing world-class research facilities and collaborative research programs in molecular imaging, proteomics, chemistry, cell and molecular biology, and bioinformatics. Working closely with the Stanford Cancer Institute, the Canary Center also brings deep experience in translating early detection research into first-in-human clinical trials – so that new discoveries can be brought to patients as rapidly as possible. For example, an ongoing clinical trial combines a new PET imaging tracer with a nasal swab and a blood draw to improve the early detection of lung cancer.
Other projects include mathematical modelling of cancer biomarker levels, early cancer detection nanosensors, smart toilet technology, proximal sampling strategies, new optical and optoacoustic imaging technologies, targeted microbubble ultrasound imaging, immune-diagnostics, longitudinal human studies of the transition from health to disease, as well as many other novel approaches. Canary Center faculty have published over 100 publications in the early cancer detection field and launched over 15 clinical trials of new early detection strategies.
Professor Sam Gambhir, ACED lead at Stanford University, said: “Continued greater investments into early cancer detection and prognostication are needed worldwide and this new alliance will bring great opportunities for truly transformative approaches to be jointly conceived, tested, and deployed. Our greatest chances in winning the war against cancer lie in tackling the front-end of the cancer problem and not after cancer is more widespread and heterogeneous.”
University of Cambridge
The Cambridge ACED centre is led by clinician scientist Professor Rebecca Fitzgerald and physicist Dr Sarah Bohndiek. It is made up of 355 members from organisations that include The University of Cambridge, the Gurdon and Wellcome Sanger Institutes, and NHS Departments.
Scientists will design, develop and deliver Clinical Infrastructure for Research in Early Detection (CuRED), a clinical facility that will enable early phase clinical trials of novel diagnostics. This will be key to test and validate early diagnostics and accelerate adoption of the most promising early detection approaches by doctors.
Ongoing research includes the development of sophisticated imaging tools to detect pre-cancerous lesions. One of these tools, developed by Dr Sarah Bohndiek working with Professor Rebecca Fitzgerald is an advanced endoscope that uses ‘hyperspectral imaging’ to reveal a range of colours beyond our vision that could highlight the early signs of cancer in the food pipe and colon.
Professor Rebecca Fitzgerald, ACED lead at the University of Cambridge, said: “Early detection is an area of research that hasn’t been given the attention it deserves. This alliance will allow the field to gain momentum, so the sum of its members will be greater than its parts.
“In Cambridge we will work on essential clinical trials that will result in faster implementation of new early detection strategies and diagnostics, making a real difference to the lives of patients.”
OHSU Knight Cancer Institute’s CEDAR Center
The OHSU Knight Cancer Institute ACED centre is led by Dr Sadik Esener, the director of the Cancer Early Detection Advanced Research (CEDAR) center and Wendt Family Endowed Chair in Early Cancer Detection at the Biomedical Engineering Department at Oregon Health & Science University (OHSU).
The OHSU Knight Cancer Institute’s CEDAR center is based at OHSU. Its mission is to detect and stop lethal cancers at the earliest possible stage.
The center works to successfully integrate a biological understanding of early diseases with novel technologies that will detect them. CEDAR pioneers early detection discovery with world-class research capabilities that include: microscopy facilities at the Oregon Center for Spatial Systems Biology; immuno-oncology and genomics research in the Cell, Developmental & Cancer Biology department; and a strong emphasis on precision oncology, multiscale imaging and high-performance computing at the OHSU Knight Cancer Institute.
The pillars of CEDAR’s approach to early detection research include population health (the accrual of longitudinal cohorts to understand risk stratification); liquid biopsy (working to discover biomarkers in proximal fluids using multi-omic approaches); technology development (to provide low-cost, minimally invasive screening and diagnosis techniques); early biological research (to interrogate the basic biology involved in the transition from pre-malignant to lethal malignancies, with an emphasis on systems biology and the development of experimental model systems of early cancer); therapeutic interventions (to include gene editing, silencing, or other precision interventions to prevent the development of lethal disease); and early detection economics and business models (to prove the advantages of cancer early detection to healthcare providers and payers).
Dr Sadik Esener, ACED lead at the OHSU Knight Cancer Institute, said: “In order to maximize the benefits versus harm associated with early detection, we need to develop precise detection and treatment of early aggressive cancers; this requires close cross disciplinary collaboration across the globe. ACED brings together leading institutions and innovative scientists from around the world ready to dedicate time, energy, and resources to take on this important challenge.”
The UCL ACED centre is led by Professor Mark Emberton and hosts 24 co-investigators across UCL and partner NHS trusts, with access to over 200,000 patients for clinical trials.
Scientists will drive research to integrate modern imaging techniques with non-imaging biomarkers such as blood and urine tests. For example, an ongoing project called Re-IMAGINE, combines information from MRIs with urine tests to improve the detection of prostate cancer. Combining information in this way could make diagnosis and prognosis much more accurate.
Professor Mark Emberton, ACED lead at UCL, said: “We desperately need to be able to detect cancer at a point when the disease can be cured without creating needless anxiety for patients or a burden to the health system.
“To achieve this, we need to seize upon the excellent work already being done in advanced imaging technologies and artificial intelligence, to understand how this can developed for use in hospitals. When work was once happening in isolation the Alliance will bring expertise together across institutions to take a holistic approach to detecting cancer earlier.”
University of Manchester
The University of Manchester ACED centre is led by Professor Rob Bristow, Director of Manchester Cancer Research Centre, and Professor Gareth Evans, BRC Cancer Prevention & Early Detection Lead. This group draws on the research power of the Cancer Research UK Manchester Institute and Centre, Manchester Cancer Research Centre, the University of Manchester, The Christie NHS Foundation Trust, Manchester NHS Foundation Trust (MFT), the Manchester Centre Cancer for Biomarker Sciences and the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).
Manchester will develop its Manchester Early Recognition of Cancer and Decision Options (MERCADO) programme to drive clinical translation of early detection research, offering a world-first NHS early detection testbed with access to more than 4 million people. The operational hub will help to reduce overdiagnosis in low-risk individuals, find personalised early detection strategies and reduce late cancer diagnoses in underserved populations who may suffer from multiple diseases.
Ongoing research includes liquid biopsy work, led by Professor Caroline Dive CBE, BRC Precision Medicine Lead. Her team, alongside chest physician Dr Phil Crosbie, BRC Early Detection Co-Lead, hope to develop a simple blood test that can detect lung tumours by detecting wayward lung cancer cells escaping into the blood circulation. The team will also study the effect of the immune system in early lung cancer development.
Professor Emma Crosbie BRC Early Detection Programme Lead, and Professor Gareth Evans will try and predict the earliest signs of endometrial and breast cancer. They will study cancer signals in urine and vaginal fluid and develop a test that could one day be used in GP surgeries, like a pregnancy test. They will also use a genetic ‘spit’ test to find young women at the highest risk of aggressive breast cancer and screen them for earlier curative treatment.
The Manchester teams will also create living tissue banks of pre-cancerous tissues to find ways to combat aggressive cancer gene activation and use artificial intelligence to bring together multiple tests that may be superior to any one test alone.
Professor Rob Bristow, a prostate cancer specialist and ACED lead at the University of Manchester, said: “Our vision at Manchester is to make early detection a reality for all patients, giving them the best chance of surviving their cancer, or better yet, avoiding it altogether. The best way to do this is to focus the new targeted tests in high-risk populations.
“Additionally, cancer diagnoses must be made earlier as many patients suffer from multiple health conditions including diabetes and heart disease. If diagnosed at an earlier stage, you could improve cancer survival before other diseases limit treatment choice and the chance of cure.”