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This CRUK-funded programme led by Professor Ellie Barnes will characterise the pre-cancerous liver microenvironment and integrate multi-modal technologies to develop and refine strategies for translatable liver cancer risk prediction and early detection.

Background

Liver cancer, of which hepatocellular carcinoma (HCC) is the commonest form, is a major global health problem, with 854,000 new cases and 810,000 deaths/year1. Liver cancer is the fastest rising cause of cancer death in the UK2 and it is projected that by 2030, HCC will be the 3rd leading cause of cancer deaths in the USA, surpassing breast, colorectal and prostate cancers3. One reason why mortality is so high is that the majority of HCCs are diagnosed at a late stage when treatment is not effective. The proportion of people surviving for 1 year after a stage 1 compared to a stage 4 liver cancer diagnosis decreases from 78% to 20%4. Therefore, strategies for the earlier detection of HCC are urgently required.

The risk of liver cancer is increased by viral hepatitis infections, alcohol and obesity (associated with chronic conditions such as non-alcoholic fatty liver disease), causing the immune system to attack the liver leading to scarring and liver cirrhosis. Monitoring of people with these conditions can reduce mortality but current diagnostic tests for HCC fail to detect cancer in many cases. Furthermore, only a small fraction of people with cirrhosis go on to get HCC and so better risk prediction is needed to more efficiently target surveillance to those at the highest risk of developing cancer.

Aims

The DeLIVER research programme aims to better understand the pre-cancerous changes in the liver and use this knowledge to inform new technologies for early HCC detection. To achieve this, they will test the hypothesis that HCC is primarily driven by liver microenvironmental (immune, metabolic, stromal) processes rather than genetic mutations. The DeLIVER team will use state-of-the-art multiparametric imaging, host and viral genetics, and liquid biopsy technologies, such as TAPS, to identify the earliest indications of HCC by studying people at high-risk of developing HCC over several years and those with early HCC.

Team

A circos plot showing the partners and the many joint publications of DeLIVER team members. The partners are: Oxford University: Translational Gastroenterology Unit (E Barnes, J Cobbold, E Culver, S Leedham, R Peters), Radcliffe Department of Medicine (M Pavlides, J Tomlinson), Department of Primary Care Health Sciences (J Hippisley-Cox), Nuffield Department of Medicine (R Fischer, B Kessler, X Lu, P Klenerman, P Matthews, J McKeating, C Song), Department of Statistics (A Ansari), Big Data Institute (G McVean, T Nichols, B Schuster-Böckler), Department of Oncology (A Blake), Department of Chemistry (J McCullagh); OncImmune (I Macdonald), Perspectum (R Banerjee, M Brady, M Kelly), Roche (D Morgenstern, L Harper), IPDX (C Neuman); Other* (H Innes, P Jepsen, D Mann, A Miners, H Reeves, P Vickerman); Nottingham (G Aithal, W Fateen, S Francis, W Irving) . DeLIVER members from all but 3 partners/departments have published joint publication(s) with other member(s) in other partners/departments.

 

Figure: A circos plot showing the DeLIVER team members and their affiliations, and the extensive established working relationships with demonstrable outputs. Abbreviations: BDI, Big Data Institute; NDM, Nuffield Department of Clinical Medicine; RDM, Radcliffe Department of Medicine; TGU, Translational Gastroenterology Unit. *Other collaborating Universities are Glasgow Caledonian University (Innes), Aarhus University, Denmark (Jepsen), London School of Hygiene and Tropical Medicine (Miners), Newcastle University (Mann, Reeves), University of Bristol (Vickerman).

 

This Oxford-led multidisciplinary team involves many OxCODE researchers, and researchers from Nottingham University, Newcastle University, Glasgow Caledonian University, University of Bristol, Aarhus University (Denmark) and the London School of Hygiene and Tropical Medicine. Together they have expertise in cancer biology, clinical hepatology, inflammation and infection, chemical biology, liquid biopsy technologies, multiparametric liver imaging, big data science, mathematical and statistical modelling, primary care health science, and health economics.

They will be supported by industry partners Roche Diagnostics, Perspectum Diagnostics, OncImmune and IPDx. DeLIVER will receive patient input from the British Liver Trust and the Hepatitis C Trust.

 

References

  1. Global Burden of Disease Liver Cancer Consortium, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol 2017;3(12):1683-91. doi: 10.1001/jamaoncol.2017.3055
  2. CRUK
  3. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155
  4. Office for National Statistics

 

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