Liver disease is increasingly common. Viral infections, alcohol excess and rising levels of obesity and type 2 diabetes are partly to blame. All of these increase the risk of developing primary liver cancer, also known as hepatocellular carcinoma (HCC). We believe that our immune system, which helps us fight infections and cancers, is suppressed in people with liver disease. This increases the chance of people affected by liver disease developing liver cancer. It also increases the likelihood of treatment for the cancer being resisted and the cancer returning afterwards.
We want to record information about patients with liver disease and compare this to similar patients with primary liver cancer (HCC). As part of this project, we will run a clinical trial at selected hospitals with a specialist interest in this area of liver cancer. Patients who consent to take part in the study will donate blood samples, answer lots of questions about them and their health, and donate "left over" liver samples following standard-care procedures. Our team of academic experts will then study all of the data which will lead to a greater understanding of HCC, and will inform future research.
If we could understand how to switch the immune system back on, we could improve responses to treatments for liver cancer. There is a new class of anti-cancer ‘immunotherapies’ which do just that. But early studies suggest that these only work for about 15-20% of people.
We want to work out why some people respond to treatments and some people don’t, so that we can convert ‘non-responders’ into responders.
HUNTER is a collaboration of 11 Universities from the UK, Spain and Italy funded through a partnership between Cancer Research UK, Fondazione AIRC and Fundación Científica de la Asociacion Española Contra el Cáncer.
Deciphering the immunological landscape of HCC
Professor Llovet and his team at L'Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) will take their initial discovery of the different existing HCC immune profiles to the next level using a multi-omics (genomics, transcriptomic, and immunomics) approach to analyse HCC tumours and matched non-tumour tissues.
They hope to identify distinct immune profiles of HCC tumours that correlate with the different responses of HCC patients to immunotherapies.
Preclinical model platform development in HCC
Dr Bird and the team at The Beatson West of Scotland Cancer Centre will lead on the creation of preclinical models that more accurately reflect the emerging subtypes of HCC based on molecular classification and associated immune profiles.
They will develop in-vivo models to enable the study of immune or combination therapies.
Breaking immunosuppressive networks in HCC
Professor Maini will lead on the integration of the different projects, to develop and validate state-of-the-art testing of novel mechanistic and therapeutic insights into the immunotherapy of HCC.
Utilising fresh HCC tissue samples collected in the clinical trial, and molecular targets shortlisted in other projects, will develop new insights into immunosuppressive networks in HCC, while testing the robustness and application of the pre-clinical models developed as part of HUNTER .
Discover more about what our HUNTER researchers are working on
Research by Amy Collins, PHD student funded by the William E Harker Foundation
A new human liver cancer culture model: precision cut liver slices (PCLS)
Observing the interactions between cells has previously been limited using cell culture and animal models. Amy Collins has been creating a human liver cancer culture model that recreates the interactions between cancer cells.
Geh D, Watson R, Sen G, et al. COVID-19 and liver cancer: lost patients and larger tumours
Primary liver cancers and the impact of COVID-19
This study focused on the impact of the COVID-19 pandemic on patients with primary liver cancer in the North East of England and Cumbria.
We found that the pandemic resulted in a 37% reduction of new HCC cases being detected in our region, with the majority of cases presenting symptomatically with larger tumours and fewer being detected by surveillance or as part of routine care.
Research by Maja Laszczewska, HUNTER Research Technician
Generating primary liver cancer cell lines from human tissues
Maja Laszczewska has been making use of surplus tissue from human liver cancer biopsies and resections. She has successfully generated cell lines and has been able to characterise the cells she has been growing using a variety of different cell-surface markers.
Study run by Professor Helen Reeves, Physio Dr Kate Hallsworth, Sports Scientist Dr Sam Orange and Research Technician Misti McCain
TELEX - telehealth for patients with liver cancer
The TELEX-Liver Cancer study aims to see whether it is feasible to deliver live, online, home-based exercise to patients (aged 60+ years) with liver cancer and to assess whether exercise can improve quality of life, fatigue, and physical fitness/strength.
Research by Fanni Palinkas, MRC DiMeN PHD student with industrial partner Astra Zeneca
DNA-PK as a treatment biomarker for locoregional therapies
Trans-arterial chemo-embolisation (TACE) is a locoregional therapy used to treat some intermediate stages of HCC, however sometimes TACE causes harm and is not always effective.
Overexpression of the biomarker DNA-PK (a DNA-dependent protein kinase catalytic subunit) in biopsy tissue from patients with HCC has been associated with a poorer response to TACE. Having a liver biopsy has risks associated with it therefore we want to look at less invasive blood samples as a tool for predictive purposes.
Previous attempts to robustly detect DNA-PK in serum have failed. Our aim is to explore mRNA transcripts in extracellular vesicles (EVs) as a liquid biopsy tool for HCC patients.
Exploration of ‘liquid biopsy’ biomarkers for HCC
There are currently limited screening tests for the early detection of liver cancer. Therefore, HCC is typically detected at an advanced stage when symptoms arise. Due to late stage detection traditional cytotoxic therapies are poorly tolerated and medical therapy options are limited due to the lack of clinically useful biomarkers.
Our team has a keen interest in developing less invasive liquid biopsy tools – focused on tumour products (cells and nucleic acids – DNA, RNA) that are released into the circulation.
Research by Dr Daniel Geh, clinical PhD student funded by the Newcastle Cancer Research UK (CRUK) Clinical Academic Training Programme
Neutrophils as potential therapeutic targets in hepatocellular carcinoma
Neutrophils are the most common white blood cell and are the immune systems first responders to infection and injury.
A growing body of evidence points to neutrophils as playing an important role in the development, progression and potential treatment of liver cancer.