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Very aggressive forms of cancer: This protein promotes pancreatic cancer


Protein promotes the development of pancreatic cancer

While advances in prevention, early detection and therapy have reduced mortality rates for most other cancers, they have been increasing steadily in pancreatic cancer. Pancreatic carcinoma is one of the most aggressive types of cancer and has so far been difficult to treat. An earlier diagnosis would be helpful. Researchers have now found that a certain protein promotes the development of pancreatic cancer.

More and more people are dying from pancreatic cancer

According to experts, there are more and more cases of pancreatic cancer in Germany. Mortality rates are increasing dramatically. However, there has been progress in the scientific understanding of the development of carcinoma at the molecular level in recent years. In addition to certain risk factors, genetic changes also play a role. Researchers have now found that a certain protein promotes the development of pancreatic cancer.

Abnormal amount of a certain protein

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

This results in an abnormal amount of the p62 / SQSTM1 protein, which adversely affects the pancreatic cells and, as a result, causes the tissue changes that develop into pancreatic cancer, according to a statement from the university.

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

Diagnosis is often late

Pancreatic cancer hardly causes any symptoms at first, which is why the diagnosis is usually only made at an advanced stage.

If the classic symptoms such as abdominal pain, loss of appetite, diarrhea, nausea and vomiting occur, in many cases treatment success can no longer be achieved. Less than 20 percent of the patients are still operable.

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

Carcinoma can develop from this later with a one percent probability.

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

Autophagy disorder

How all these factors relate to each other and the mechanisms behind them has so far been unclear.

The team of Austrian and American researchers has now succeeded in proving in a study using an animal model and human cell material that a disorder in the autophagy of the cells is involved in the development of the carcinoma.

Autophagy is the necessary process in the body in which cells carry out a kind of recycling and break down and reuse their own components, as well as reject bad proteins and cellular waste.

If there is such a disorder, which can be caused, for example, by smoking and being overweight, this worsens the genetically caused existing lesions on the pancreatic cells, the function of which is the production of digestive enzymes.

There is then an unusual accumulation of the protein p62 / SQSTM1, which is typically increased in chronic pancreatitis and in the precursor lesions (pancreatic intraepithelial neoplasms 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 turns into pancreatic cancer.

Initially, the protein p62 causes another protein called NRF2 to be transferred to the cell nucleus. This in turn stimulates the production of the MDM2 protein.

Increased MDM2 converts azinar cells, which have certain cancer-causing gene mutations, into proliferating duct cells. The malignant pancreatic tumor, the ductal adenocarcinoma of the pancreas, grows from this.

The result of the study suggests that a new therapeutic approach could be the treatment of autophagy, since most of the risk factors mentioned disrupt this process.

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

Better therapy options through earlier diagnosis

Other research institutions have also worked in recent years on how pancreatic carcinoma can be recognized earlier and treated better.

Scientists from the German Cancer Research Center (DKFZ) found that the ability to metastasize in pancreatic cells is often 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.

US experts, on the other hand, 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 of the insights that lead to early detection of the disease can improve treatment options. (ad)

Author and source information

Video: Pancreatic Adenocarcinoma - Mayo Clinic (September 2020).