Saturday, August 31, 2013

New insight found in the cellular process of development of liver cancer

The death of numerous liver cells in the context of chronic inflammation due to apoptosis, a form of programmed cell death, can promote the formation of tumor cells in the liver. This new insight by scientists significantly contributes to a better understanding of cellular processes in liver cancer development and thereby opens up new therapeutic approaches. This was reported in the current issue of the scientific journal 'Cell Reports'. Liver cancer due to chronic inflammation: tumour growth follows programmed cell death (apoptosis)

Liver cancer (Hepatocellular Carcinoma, HCC) usually arises as the result of a chronic, inflammatory liver disease. The most common causes are excessive alcohol consumption as well as a high-fat diet and also chronic infection with the hepatitis viruses B and C. In the course of the inflammatory process, the liver cells (hepatocytes) die more frequently due to programmed cell death. The result is increased cell growth, also referred to as compensatory proliferation, which can lead to tumour development.
A distinction is made between the two most important forms of self-induced cell death, namely apoptosis (programmed cell death) and necroptosis (programmed necrosis), which are based on different cellular mechanisms. Until now, it was not clear which form of cell death is decisive for the development of malignant liver tumors. The scientists have now been able to verify that apoptosis precedes the development of abnormal liver cells. The scientists showed this using mouse models. Moreover they discovered that in contrast, necroptosis prevents uninhibited cell proliferation and consequently the development of liver cancer.

These findings could form the basis for new approaches to therapy for liver cancer, which until now has been a form of cancer that cannot be adequately treated and that kills 800,000 patients around the world each year. We now know which cellular signalling pathways are involved in liver tumor development. As a next step, the scientists want to develop new treatment options using this information, for example, by attempting to pharmaceutically block the apoptosis itself or its signalling pathways. But any new therapy can also cause undesirable effects: In their experiments, the scientists saw that blocking apoptosis under inflammatory conditions can result in bililary obstruction (cholestasis) in the context of liver inflammation.

In the near future, the scientists want to verify their findings on the development of liver cancer and search for active substances that inhibit apoptosis while simultaneously causing the mildest possible side effects. The objective is to further develop the research in order to provide concrete benefits for society.


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