Crucial mechanism researched: How liver cancer develops

Enzyme plays an important role: How liver cancer develops
Liver cancer is the second leading cause of cancer-related death worldwide and the fastest growing cancer. Researchers have now discovered a central mechanism for how liver cancer develops. The new findings are important, among other things, for the treatment of patients with chronic liver diseases.

Second most common cause of cancer-related death
According to health experts, liver cancer is the second leading cause of cancer-related death worldwide and the fastest growing cancer. An international team of researchers has now discovered a central mechanism for how liver cancer develops. A certain enzyme plays an important role in this.

Liver cancer from chronic liver diseases
In most cases, the tumor develops in patients with chronic liver diseases. Since liver cancer and cirrhosis are often due to chronic infections with hepatitis viruses, medical professionals are repeatedly calling for routine tests to uncover the hidden contagions.

The risk of liver cancer also increases due to a so-called fatty liver, which is due, for example, to diet-related or genetically caused fat metabolism disorders 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 promotes tumor development
Although it has long been known that liver cell cancer develops particularly frequently after the liver has been damaged by chronic disease, it has so far 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 tumor development.

The more cells die, the more the remaining cells have to divide. In these divisions, they accumulate mutations: a breeding ground for liver cell cancer, the DKFZ wrote in a message.

Enzyme plays an important double role
The scientists found that the enzyme caspase 8 has an important double function in this process. The investigations were initially carried out on mice. Patient data show that the results are transferable to humans.

On the one hand, caspase 8 is important for programmed cell death, called apoptosis. Apoptosis protects degenerate cells by eliminating themselves. For a long time, the motto was: apoptosis protects against cancer.

The current study, which was published in the specialist magazine "Cancer Cell", shows that this only applies to every single cell, but not to the entire tissue of the liver.

Mutations in DNA
If too many cells undergo apoptosis at the same time, this promotes cancer development. The reason: the remaining liver cells then have to divide much more to compensate for the loss of tissue.

"Liver cells are not used to such high division rates over a long period of time, they are overwhelmed and make mistakes," explains Mathias Heikenwälder from the DKFZ in Heidelberg.

Patients with chronic liver inflammation therefore accumulate numerous DNA damages - the breeding ground for cancer.

Because the more mutations sneak into DNA, the more likely it is that the cell will break out of its normal life cycle and divide and grow unhindered.

Detect and repair damage
However, Caspase 8 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 of each other. So you can also influence them separately.

This is particularly important for the treatment of liver cancer or chronic liver diseases. If you completely eliminated the enzyme Caspase 8, you would prevent programmed cell death and the development of cancer.

At the same time, however, the cell would also be robbed of a DNA repair mechanism. It is important to avoid that.

Important for the treatment of patients with liver diseases
The scientists next want to examine whether there are similar processes in other types of cancer and examine the dynamics of the mechanism in more detail.

"We do not yet know when and why Caspase 8 and the other molecules come together and look for DNA damage," said Heikenwälder. "There are still many questions open."

UZH professor Achim Weber from the Institute of Pathology and Molecular Pathology at the University Hospital Zurich said in a communication that the results of the study are not only relevant for basic research:

"Our results have important implications for the clinic - on the one hand for the treatment of patients with chronic liver diseases and on the other hand for the application of cancer drugs that induce cell death." (Ad)

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