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Pancreatic cancer: what makes tumors so aggressive
There are more and more cases of pancreatic cancer in Germany. Pancreatic carcinoma is one of the most aggressive types of cancer and has so far been difficult to treat. Researchers have now found out what makes the tumors so aggressive.
Extremely aggressive form of cancer
While advances in prevention, early detection, and therapy have reduced mortality rates for most other cancers, they have increased dramatically in pancreatic cancer. Pancreatic carcinoma is one of the most mortal cancers in the world. Researchers have now found out what makes cancer so aggressive.
Diagnosis is often late
"Pancreatic cancer causes no symptoms for a long time and is therefore only discovered late," explained the CEO of the German Cancer Research Center (DKFZ), Michael Baumann, in an older message.
"The tumors spread metastases very early on and, to make matters worse, develop resistance to chemotherapy very quickly," says the expert.
Scientists at the DKFZ found out years ago that a specific enzyme is responsible for the resistance of the tumors.
And an international team of researchers found that the aggressive form of cancer is promoted by a certain protein.
A research team from the Technical University of Munich (TUM) and the German Cancer Consortium (DKTK) have now also found an explanation for the aggressiveness of the tumors.
Genetic causes so far unclear
So far, scientists have failed to relate properties of pancreatic cancer, such as its aggressiveness, to changes in the genetic makeup of the tumor, known as mutations.
In addition, pancreatic cancer forms metastases much faster than other cancers. Here too, the genetic causes are still unclear.
A team led by Prof. Roland Rad and Prof. Dieter Saur at the TUM University Hospital on the right of the Isar and the German Cancer Consortium has come a decisive step closer to both problems.
With the help of various mouse models to study pancreatic cancer, they succeeded in uncovering the molecular pathways of tumor development in detail. In this way you can understand how different properties of the disease arise.
The study was recently published in the journal "Nature".
Tumor cells have several faulty copies of a cancer gene
Healthy cells in humans have two copies of each gene. For their experiments, the researchers mutated one of the two copies of the kras gene in mice.
The gene plays an important role in cell proliferation and is activated in 90 percent of all human pancreatic tumors. Such genes are also known as cancer genes or oncogenes.
The team led by Roland Rad made a surprising discovery: The mutated gene was often duplicated in the very early stages of cancer.
If a tumor had not doubled the mutated Kras gene copy, the researchers discovered copies of other cancer genes.
“It seems that the cell has to increase the growth signal through the additional gene copies. This model of dose enhancement during tumor development has not yet been taken into account, ”Sebastian Müller, first author of the study, said in a message.
He added: "We were also able to show that with an increased number of mutated Kras copies, the aggressiveness and the ability to metastasize increased."
Disruption of the body's protective mechanisms determines the evolution of cancer
Normally, healthy cells have their own protective mechanisms so that mutations do not accumulate. So why were the cells able to achieve this dose increase at all without being prevented from doing so?
“This shows the importance of mouse models. They enable us to comprehensively observe and experimentally check the extraordinarily complex processes involved in molecular cancer development: from healthy cells to cancer precursors to aggressive tumors and their spread into various organs, ”says Prof. Dieter Saur.
After the Kras mutation caused by the researchers, further mutations first appeared in so-called tumor suppressor genes. In order to prevent the development of a tumor cell, a healthy cell has a number of such protective genes.
A fundamental finding of the researchers was: Depending on which tumor suppressor gene was affected and how severely its function was impaired, either the mutated Kras gene or another cancer gene is duplicated.
The most important development steps are cleared up
A tumor can only develop in the end by switching off the cell's protective mechanisms and then increasing the dose.
Which path the cell takes and which genes are involved then decisively determined the properties of the pancreatic tumor.
The model of “dose enhancement” makes it possible for the first time to define genetic patterns that explain its aggressiveness and metastasis.
“We have evidence that our discovery is a fundamental principle in the development of tumors and is also important for other types of cancer. We are now investigating the extent to which these new insights into tumor biology can be used to develop new therapy strategies, ”said Prof. Roland Rad. (Ad)