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Ellie Barnes, Emma Culver and Paul Klenerman are recruiting a DPhil candidate for the funded DPhil in Cancer Science commencing in October 2023.

A studentship to work with the DeLIVER team is available through the DPhil in Cancer Science Programme, funded by Cancer Research UK.

The project is entitled "Understanding the hepatic immune and molecular environment in the development of hepatocellular carcinoma" under the supervision of Ellie Barnes, Emma Culver and Paul Klenerman.

All places are fully funded at the home rate, including salary/stipend, University and College fees, and a research consumables budget. International candidates are eligible but will need to source funding to meet the remaining fees. For more information about funding, see the Oxford Cancer website.

Applications must be completed on the University of Oxford graduate application system by 9th December 2022. Interviews will take place in January 2023.

For more information about the available projects, eligibility and application procedure, see the Oxford Cancer website.

Lay Summary

Background:

Cancer that begins in the liver (hepatocellular carcinoma) is one of the fastest rising and fourth commonest cause of deaths due to cancer world-wide. Liver cancer is usually associated with liver viral infections, alcohol and obesity, causing the immune system to attack the liver leading to scarring and liver nodules (liver cirrhosis). We know that changes throughout the cirrhotic liver tissue are the major risk factor for liver cancer, but we do not understand the nature of these changes, or why and when some people develop cancer and others do not. So far, little effort has been made to characterise these changes.

Aim and methods:

We aim to better understand the changes within the liver that lead to cancer so that strategies for early cancer detection can be applied. We plan to take a sample from the blood and the liver using a fine needle, from people at risk of getting liver cancer and those already with liver cancer. Fine needle sampling of the liver is considered safe and has been used to gather tissue cells for many years. We want to look at the cells in the liver to assess some of the material that is inherited (DNA) and look at chemical reactions that occur in the body that can influence how the DNA may interact with other molecules (methylation). We also want to look at the different immune cells (sequencing) and the proteins and chemicals (metabolome) in the blood and liver that have a role in inflammation and cancer development.

Outcomes:

We believe that our approach will lead to a much better understanding of the biological reasons for the development of liver cancer. We hope also that in using the best combination of the most promising tests, we will be able to identify cancer at the very earliest stages so that people can be cured.

Abstract

This project builds on recent momentum at Oxford to develop strategies to detect hepatocellular carcinoma (HCC) early when curative therapies may be applied, underpinned by a CRUK HCC early detection award-DeLIVER. The incidence of HCC is increasing in the UK and is a leading cause of death globally (1). HCC usually occurs in the setting of advanced fibrosis/cirrhosis with a “field effect” change in the liver that predisposes to cancer transformation. Less often, HCC may arise de novo, particularly in fatty liver disease (FLD) (2). Factors that are known to be associated with the development of liver cirrhosis and HCC include viral infections (hepatitis B and C viruses), non-alcoholic fatty liver disease (NAFLD), alcohol induced liver disease and iron overload (haemochromatosis). Once cirrhosis is established approximately 1-4% of people/year develop HCC However, the biological pathways that lead to the development of HCC are not understood. This proposal now focuses on understanding the changes within the liver, characterising in detail the field effect that leads to HCC transformation. Recently, we have now established the ethical framework to recruit patients with HCC and those with cirrhosis at risk of developing HCC, with diverse underlying disease aetiologies. Now, fine needle aspiration (FNA) of non-cancerous liver in patients with and without HCC will be performed to identify the liver cellular phenotypes linked to the development of HCC. Cancerous liver tissue will also be obtained where possible in a new collaboration with the department of surgery. Blood samples from the same patients will be collected and analysed by collaborators to identify genetic/epigenetic mutations in cell free DNA from peripheral blood, and metabolites from blood and urine. The overarching aim is to establish early data that will identify new methodologies that alone, or in combination, may be used for the early detection of HCC