Very aggressive forms of cancer This protein promotes pancreatic cancer

Protein favors the development of pancreatic cancer

While advances in prevention, screening, and therapy have reduced mortality rates in most other cancers, they continue to rise in pancreatic cancer. Pancreatic carcinoma is one of the most aggressive cancers and so far barely treatable. Helpful would be an earlier diagnosis. Researchers have now discovered that a particular protein favors the development of pancreatic cancer.

More and more people are dying of pancreatic cancer

According to experts, more and more cases of pancreatic cancer are registered in Germany. Mortality rates are rising dramatically. Pancreatic carcinoma is one of the most aggressive cancers and so far barely treatable. However, in recent years, there has been advances in the scientific understanding of the development of carcinoma at the molecular level. In addition to certain risk factors, genetic changes also play a role. Researchers have now discovered that a particular protein favors the development of pancreatic cancer.

Pancreatic cancer is one of the most aggressive forms of cancer and has been barely treatable so far. Helpful would be an earlier diagnosis. Researchers have now discovered that a particular protein favors the development of pancreatic carcinoma. (Image: Coloures-pic / fotolia.com)

Abnormal amount of a particular protein

A team led by laboratory doctor Jelena Todoric from the Clinical Institute for Laboratory Medicine of the Medical University of Vienna (MedUni) and molecular biologist Michael Karin from the University of California at San Diego showed in a study that a disturbed autophagy of the cells can precede the genetic changes.

The result is an abnormal amount of the protein p62 / SQSTM1, which adversely affects the pancreatic cells and as a result causes those tissue changes that develop into a pancreatic carcinoma, it says in a statement from the university.

The scientists published their results in the journal "Cancer Cell".

Diagnosis often takes place late

At first, pancreatic cancer causes little discomfort, which is why the diagnosis is usually only at an advanced stage.

If the classic symptoms such as abdominal pain, loss of appetite, diarrhea, nausea and vomiting occur, in many cases no treatment success can be achieved. Less than twenty percent of patients are then still operable.

It is known in medical research that 16 percent of healthy people and 60 percent of patients suffering from pancreatitis, or pancreatitis, suffer from so-called precursor lesions in the pancreas.

This can later develop with one percent probability of a carcinoma.

But also genetic factors, risk factors such as smoking, obesity, diabetes and chronic pancreatitis play a role.

Disorder of autophagy

However, how all of these factors are related to each other and what mechanisms are behind them has so far been unclear.

Now, the team of Austrian and US researchers has been able to prove in a study on animal models and human cell material that a disruption of autophagy of the cells is involved in the development of the carcinoma.

Autophagy is the necessary process in the body where cells perform a sort of recycling and degrade and recycle their own constituents, as well as repelling bad proteins and cellular wastes.

When there is such a disturbance, which may be caused, for example, by smoking and obesity, it worsens the genetically-caused existing lesions on the pancreatic cells whose function is the production of digestive enzymes.

This leads to an unusual accumulation of the protein p62 / SQSTM1, which is typically elevated in chronic pancreatitis and in precursor lesions (pancreatic intraepithelial neoplasm PanIN).

Development of targeted drugs

The study showed that the accumulation of p62 / SQSTM1 favors the development of early precursor lesions, the so-called acinar ductal metaplasia. As a result, a cascade of molecular activities then produces pancreatic carcinoma.

Initially, the protein p62 causes a shift of another protein called NRF2 into the nucleus. This in turn stimulates the production of the protein MDM2.

Elevated MDM2 converts Azino cells that have certain cancer-causing gene mutations into proliferating duct cells. From this finally grows the malignant pancreatic tumor, the ductal adenocarcinoma of the pancreas.

The result of the study suggests that a new therapeutic approach could be found in the treatment of autophagy, as most of the risk factors mentioned above interfere with this process.

The development of targeted MDM2 drugs could in the future prevent the development of malignant pancreatic cancer in people at high disease risk.

Better treatment options through earlier diagnosis

Other research institutions have also spent the last few years studying how pancreatic cancer can be detected earlier and treated better.

For example, scientists from the German Cancer Research Center (DKFZ) found out that in pancreatic cells the ability to metastasize is often already developed before a cell has even turned into a cancer cell.

They also found that a specific enzyme is responsible for the resistance of the tumors.

In turn, US experts found that bacteria can help diagnose pancreatic cancer.

And according to British researchers, pancreatic cancer could also be diagnosed with a urine test in the future.

All the insights that can lead to earlier detection of the disease can improve the treatment options. (Ad)