Hepatobiliary Cancer Theme

Hepatobiliary cancer is at the very core of the Scotland Centre’s mission; across the UK both Scottish men and women are most likely to get liver cancer and die from it. In the UK, cases have doubled within the last decade and continue to rise. In comparison to other cancer types, research into hepatobiliary tumours has been lagging behind. Redressing this is major focus of the Centre.

Tumours of the liver, gallbladder, and bile duct, together known as hepatobiliary cancers (HBC) present an increasing challenge for global health. The incidence these diseases is directly linked to rates of major risk factors which drive liver disease and cirrhosis becoming prevalent – including obesity and alcohol consumption. Whilst advancement in treatment options has occurred within the last 20 years, survival is still remarkably poor, especially for those patients diagnosed at an advanced stage.  For bile duct cancer (cholangiocarcinoma) this manifests in less than a quarter of patients being amenable for surgery.

Improving Detection and Therapy

Through strong joint efforts with local experts in preclinical modelling in liver disease and cancer, our team at the Scotland Centre is driven by clinician scientists that are actively involved in patient diagnosis, surgery and oncology. We are taking an integrated approach to identify these diseases earlier and provide better treatment options. The Centre greatly enhances existing research activities around local tissue resources, membership in international clinical networks, and strong data linkage within Scotland.

Although chronic liver disease can lead to tumour development, the rates for clinical monitoring are low. We are developing an interventional study, implemented via the Scottish Hepato-Pancreato-Biliary Network, which will enrol patients with liver cirrhosis to test MRI as a cost-effective method for surveillance and early detection of liver and bile duct cancer. In partnership with the scientists from our data theme, Scottish health records will identify patients most at risk of HBC. We will also gather liquid biopsies to improve our understanding of pre-cancerous tissue and to develop a bank of patient-derived disease representative cells (organoids), together with our CRUK colleagues from the early detection DeLIVER programme and HUNTER:HCC Expediter Network.

Understanding human disease better is the first step in developing a screening pipeline for novel therapies. Our aspiration is to build on in-depth knowledge from patient samples to generate clinically relevant models and refine these models through cross-species omics analyses. Ultimately, we aim to establish clinical trials based on pre-clinical discoveries in basic biology while partnering with Cancer Research Horizons and industry to develop targetable mechanism into promising drug therapy. For liver cancer, the Accelerator HUNTER network has boosted in vivo modelling through the identification of actionable mutations and generating over 30 unique and disease relevant mouse models. As a Centre team, we will prioritise the most human-relevant and challenging to treat liver cancer subtypes to identify therapeutic vulnerabilities. In cholangiocarcinoma, the mutational burden is relatively small, and our work will focus on modelling additional factors, such as inflammation, epigenetics and tumour microenvironment, that contribute to tumour formation.

Theme Members