Dutch Cancer Society grant to study how fatty liver disease can contribute to liver cancer

Delilah Hendriks, researcher from the Organoid group, Oncode researcher, and affiliated group leader at the Princess Máxima Center (the Máxima Center), has received a Young Investigator Grant from the Dutch Cancer Society (KWF). Together with researchers from the Maxima Center, University Medical Center Utrecht (UMC Utrecht), and Avans, she will study how fatty liver disease can lead to liver cancer. Additionally, they will look into the early stages of liver cancer in order to identify how metabolic changes in mutated liver cells can lead to cancer development.

Fatty liver disease is a condition that causes a build-up of excess fat cells in the liver. The disease can be caused by many factors, mainly metabolic factors and obesity, and it is a risk factor for liver cancer. At the moment roughly 30% of the global population are suffering from some type of fatty liver disease. The number of people affected is currently rising at an alarming rate, with incidence even increasing in young children. This means that more and more people will suffer from the disease in the future and it is also expected that the number of liver cancer cases will go up as a result. Hendriks mentions: “The lack of human-relevant models has hampered our understanding of the human disease biology.” Therefore, it is unclear what exactly causes the increased susceptibility to liver cancer and how best to treat liver cancer that arises from fatty liver disease.

Will human liver organoids provide a better study model?

With the grant, Hendriks will work together with Benedetta Artegiani (the Máxima Center), Ruben van Boxtel (the Máxima Center), Maria Rodriguez Colman (UMC Utrecht), and Jos Brouwers (Avans) to look into how fatty liver disease changes the liver. They will use human liver organoids, which function as 3D mini livers and mimic the shape and function of an actual liver. The researchers will model fatty liver disease in the organoids in order to study how the condition affects the liver cells. Hendriks says: “We are eager to discover signs of cellular transformation and to then start to understand the underlying mechanisms of how fatty liver disease can result in liver cancer.”

Changing the metabolism of cells can result in cancer

Many causes of fatty liver disease are related to our metabolism, examples of these include obesity and diabetes. In these cases, the metabolism of the liver cells is affected. Therefore, the researchers want to study how metabolic changes can lead to liver cancer development. They want to make use of the gene editing technique CRISPR/Cas, to introduce mutations which simulate the early stages of liver cancer. This permits them to study how the mutations can result in metabolic changes in the liver cells, and how these alterations can lead to cancer. This could eventually lead to the discovery of novel biomarkers or drug therapies.

More about KWF grants

The KWF is investing a total of 10.9 million euros across 17 new studies that focus on fundamental questions in the oncology field. 8 of these 17 studies have been selected from the proceeds of Alpe d’HuZes. The full financing decision can be found on the website of the Ducth Cancer Society (only in Dutch). This research project, led by Hendriks, received a Young Investigator KWF grant which is meant as a stepping stone for young researchers to work towards their own research line within the cancer field.

Delilah Hendriks.

Source: Hubrecht Institute