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Crucial mechanism researched This is how liver cancer develops
Liver cancer is the second most common cause of cancer death worldwide and the highest rate of cancer. Researchers have now discovered a key mechanism for developing liver cancer. Among other things, the new findings are important for the treatment of patients with chronic liver diseases.
Second most common cause of cancer death
According to health experts, liver cancer is the second most common cause of cancer death worldwide and the fastest growing incidence of cancer. An international research team has now discovered a key mechanism for developing liver cancer. A particular enzyme plays an important role.
An international research team has discovered a key mechanism for developing liver cancer. Among other things, the new findings are important for the treatment of patients with chronic liver diseases. (Image: blueringmedia / fotolia.com) Liver cancer due to chronic liver disease
In most cases, the tumor develops in patients with chronic liver disease. Since liver cancer and cirrhosis are often due to chronic infections with hepatitis viruses, doctors repeatedly require routine tests to detect the hidden infections.
The risk of liver cancer is also increased by so-called fatty liver, which is caused, for example, by dietary or genetically caused disorders of the lipid metabolism or excessive alcohol consumption.
US scientists also published a study last year that provided evidence that obesity and type 2 diabetes increase the risk of liver cancer.
Cell death favors tumorigenesis
Although it has long been known that hepatocellular carcinoma is particularly prevalent after the liver has been damaged by chronic disease, it has been unclear how these events are related at the molecular level.
An international team of scientists from the German Cancer Research Center (DKFZ) and the University of Zurich (UZH) has now shown that chronic cell death promotes tumorigenesis.
The more cells die off, the more the remaining cells have to divide. In these divisions, they pile up mutations: a breeding ground for liver cell cancer, writes the DKFZ in a statement.
Enzyme plays an important dual role
The scientists found that the enzyme caspase 8 plays an important dual role in this process. The investigations initially took place on mice. Patient data shows that the results are transferable to humans.
On the one hand, caspase 8 is important for programmed cell death, called apoptosis. By apoptosis degenerate cells protect the organism by eliminating itself. For a long time, the motto was: Apoptosis protects against cancer.
The current study, published in the journal "Cancer Cell", shows that this applies only to every single cell, but not to the entire tissue of the liver.
Mutations in the DNA
Excessively too many cells undergo apoptosis at the same time, which favors the development of cancer. The reason: The remaining liver cells then have to divide much more to compensate for the tissue loss.
"Liver cells are not used to such high division rates over a longer period of time, they are thus overtaxed and make mistakes," explains Mathias Heikenwälder from the DKFZ in Heidelberg.
Patients with chronic hepatitis therefore accumulate numerous DNA damage - the breeding ground for cancer.
Because the more mutations creep into the DNA, the more likely it is that the cell breaks out of its normal life cycle and divides and grows unhindered.
Detect and repair damage
Caspase 8, however, has a completely different function. As part of a newly identified, larger complex, the molecule is involved in recognizing DNA damage and initiating its repair.
The apoptosis and repair functions work independently. They can therefore be influenced separately from each other.
This is especially important for the treatment of liver cancer or chronic liver disease. If you completely eliminated the enzyme caspase 8, then you would prevent the programmed cell death and the development of cancer.
At the same time, however, the cell would also be deprived of a DNA repair mechanism. That is to be avoided.
Important for the treatment of patients with liver disease
Next, the researchers want to see if there are similar events in other cancers as well, and examine the dynamics of the mechanism more closely.
"So far we do not know when and why Caspase 8 and the other molecules come together and look for DNA damage," says Heikenwälder. "There are still many questions left."
UZH Professor Achim Weber from the Institute of Pathology and Molecular Pathology at the University Hospital Zurich stated in a statement that the results of the study are not only relevant for basic research:
"Our findings have important implications for the clinic - on the one hand for the treatment of patients with chronic liver disease and on the other for the use of cell death-inducing cancer drugs." (Ad)