The International Alliance for Cancer Early Detection (ACED) is a 55 million ($70 million) partnership between Cancer Research UK (CRUK) and five of the worlds foremost centres in early detection research. One year on, we look at four recently awarded research projects, which show how the Alliance is building a scientifically diverse and collaborative research community in the UK and the US, united at the forefront of cancer early detection.

Detecting and diagnosing cancer early is complex and has been hindered by scientific and clinical challenges. With a fragmented research community, limited access to early-stage tissue samples and a lack of commitment or prioritisation from industry and research funders, research progress in this emerging field has been slow.

Founded in 2019, ACED is a CRUK partnership with the Canary Center at Stanford University, the University of Cambridge, the Knight Cancer Institute at Oregon Health and Science University (OHSU), University College London and the University of Manchester. The Alliance brings together leaders in early detection research in a collaborative community, to work together to generate novel ideas and share knowledge. Its research strategy spans the scientific pipeline; from understanding the fundamental biology of early stage disease to developing new technological approaches and implementing early detection strategies through clinical trials and health systems.

The five ACED Member Centres can access funding in three areas: core funding for building capacity; shared infrastructure funding for training, networking and research platforms/resources; and joint funding for collaborative research activities. In its first year, 14 research projects have been funded including 3 Project Awards, 9 Pilot Awards and 2 Skills Exchange and Development Travel Awards.

Project Award, led by: Georgios Lyratzopoulos, University College London; Antonis Antoniou, University of Cambridge; and Ruth Etzioni, Oregon Health and Science University

Currently, about 90% of cancer patients in England are diagnosed after symptom onset. Appropriately assessing the risk of undiagnosed cancer in patients who present with new symptoms is therefore critical for achieving earlier diagnosis. Yet our approach to classifying such risk is imperfect. Clinical guidelines do not encompass lower-risk symptoms, which are the presenting features of about half of all patients. Further, among patients who do present with high-risk symptoms mandating urgent referrals, only one in 12 are found to have cancer. In 2019, the last pre-pandemic year, about 2 million patients in England who were investigated urgently were found not to have cancer, and improvements in risk classification could allow NHS diagnostic services to be used more efficiently in the future.

To improve upon these two problems, and drawing on their statistical, computational and health informatics expertise and that of their collaborators, Georgios, Antonis and Ruth will utilise rich electronic health record data to develop algorithms to risk-stratify patients presenting with symptomatic-but-as-yet-undiagnosed cancer. In particular, they will aim to incorporate information on the patients medical history (with regard to diagnostic investigations, morbidities and past medications) into their algorithm, together with information on underlying susceptibility to cancer due to lifestyle-related exposures or genetic risk.

Beyond improving the assessment of cancer risk, this project will also facilitate future early detection research by delivering reproducible operational definitions (otherwise known as patient record phenotypes), that can be used by other members of the Alliance and the scientific community at large when using novel patient record datasets in the UK, the US and globally.

Project Award, led by: Marc Tischkowitz, University of Cambridge; Allison Kurian, Canary Center at Stanford for Cancer Early Detection; and Gareth Evans, University of Manchester

CanRisk is a validated cancer risk assessment tool which combines genetic, lifestyle, clinical and imaging data to calculate an individual risk estimate for women with high-risk mutations in BRCA1 and BRCA2. Currently the women who carry these mutations are given wide cancer risk estimates. For example, someone might be told they have a 5085% lifetime risk of developing breast cancer. But for that individual, they really want to know is it nearer to 50% or 85%, or perhaps even outside that range?

Now, with an ACED Project Award, Allison, Gareth and Marc are collaborating to determine how CanRisk can be best used in the clinic. The researchers will recruit patients via genetics clinics in the UK and US, randomising them between a personalised or conventional risk estimate group. They will follow patient uptake of cancer surveillance and risk-reducing mastectomy, as well as analysing psychological and economic measures. The international nature of this project, across three centres in two different countries, will enable the team to investigate the difference in early detection uptake across different health systems. Moreover, it will benefit the wider research community by establishing a risk-stratified cohort that could form the basis for further early detection studies in the future.

Pilot Award, led by: Alice Fan, Canary Center at Stanford for Cancer Early Detection; Emma Woodward, University of Manchester; and Eamonn Maher University of Cambridge

Platelet transcriptomes have the ability to respond to the presence of different cancer types by splicing RNA into specific patterns. Rapid platelet turnover and the ability to propagate this transcriptional response throughout the entire platelet population may prove to be a very sensitive biomarker for cancer.

Alices lab at Stanford has generated promising preliminary data for a candidate platelet transcriptomic signature for early-stage renal cell cancer. With this ACED Pilot Award, Emma, Eamonn and Alice will join forces to investigate if this signature can be used to complement diagnostic imaging for the early diagnosis of kidney cancer in high-risk families with hereditary renal cell carcinoma syndromes.

Skills Exchange and Development Travel Award, Christian Hoerner, Canary Center at Stanford for Cancer Early Detection

Isolating platelets from fresh whole blood for transcriptome profiling can be very tricky. Platelets activate very easily and contain only tiny amounts of RNA, 10,000 times less than white blood cells. Christian, a researcher in Alices lab, has been awarded a Skills Exchange and Development Travel Award to share his platelet isolation protocol with the Manchester and Cambridge teams. This award directly addresses a key aim of the ACED Alliance to drive the exchange of knowledge between teams and minimise duplication.

COVID-19 has undoubtedly had a significant impact on the first year of the ACED Alliance, delaying the start of many projects when labs were forced to shut, and clinicians redeployed to respond to the virus.

Alliance members have rapidly had to adapt the way they come together to create new collaborations and ideas. Planned in-person networking events were quickly reimagined as virtual ones and members have held numerous online meet-and-greet events on topics including model systems, epidemiological approaches, non-invasive sampling, nanomedicine and career development for early career researchers. We know of at least two successful grant applications that were brokered at virtual events, as researchers continue to build connections across multiple disciplines and centres.

As the Alliance develops, there will be many opportunities to work with us, including:

If you're interested in working with us, we'd love to hear from you.

By David Crosby, Head of Prevention and Early Detection Research, Cancer Research UK

Sanjiv Sam Gambhir, MD, PhD, professor and chair ofradiologyat theStanford School of Medicineand an internationally recognised pioneer in molecular imaging, died of cancer on 18 June 2020.

Sam was a giant in the field of early detection of cancer, well known for the development of positron emission tomography reporter genes. His work was novel and wide-reaching, developing multiple other approaches to early detection of disease, including microbubbles and immunodiagnostics. Through his work as director of the Canary Center at Stanford for Cancer Early Detection, he was a passionate advocate of devising ambitious plans to deliver paradigm-changing opportunities for early detection and a champion of ACEDs mission. He was a critical founding member of the Alliance Executive Board.

It is certainly the case that ACED would not exist without Sam. He was the inspiration that led directly to the concept of ACED, and only through his ingenuity and positivity did that concept develop into the flourishing reality that ACED now is. We, and the world, are greatly diminished for his loss.

Sam was posthumously given the Don Listwin Award for outstanding contribution to the field of cancer early detection at this years Early Detection of Cancer Conference. Before his death, Sam was also awarded the Deans Medal, the University of Stanford School of Medicines highest honour, for his revolutionary contributions to biomedicine and to human health. To find out more about Sams life and his legacy watch the Deans Medal Tribute video.

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ACED one year on: a promising first year for the early detection research alliance - Cancer Research UK