Cancer therapy: New treatment approach against aggressive tumors

Cancer therapy: New treatment approach against aggressive tumors

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New approaches to cancer therapy discovered

The number of new cancer cases in Germany has almost doubled since 1970. In addition to the surgical removal of the tumors, radiation and chemotherapy are currently also available as treatment options. However, researchers have now discovered completely new approaches to cancer therapy.

The number of cancers is increasing

More and more people are getting cancer: According to the World Cancer Report by the International Agency for Research on Cancer (IARC), 20 million new cases of cancer could occur each year by 2025. There are more and more new cancer cases in Germany. The number of new diagnoses in Germany has almost doubled since 1970. Patients are usually treated with surgery, chemotherapy and / or radiation. However, researchers have now discovered completely new approaches to cancer therapy.

Malignant vascular tumors with an aggressive course

Angiosarcomas are rare malignant vascular tumors with an aggressive course. In addition to surgical removal, radiation and chemotherapy are currently available as treatment options.

However, malignant vascular tumors have so far mostly responded poorly to such therapies.

A team of cancer researchers from the University Medical Center Göttingen (UMG) has now discovered a fundamentally new approach to how common chemotherapy could be more effective against rare vascular tumors.

The scientists found that particularly aggressive angiosarcoma cells specifically activate a signaling pathway that makes the cells almost insensitive to deadly oxygen stress and thus extremely resistant to chemotherapy.

The research results were recently published in the journal "Clinical Cancer Research".

Changing tumor cells with medication

"We wanted to know whether it is possible to use drugs to change the tumor cells so that they can be combated again by oxygen stress," said Dr. Vivek Venkataramani, Clinic for Hematology and Medical Oncology and Institute for Pathology of the UMG, in a message.

He and his team of researchers have found a way to achieve this, at least in a test tube: by combining the active ingredient "pazopanib" with common chemotherapy, oxygen stress could be generated in the tumor cells, effectively killing the cells.

The active ingredient has already been approved for use in tumor patients and could therefore soon go into clinical trials as a combination therapy with conventional chemotherapy in angiosarcoma patients, "said Prof. Dr. Philipp Ströbel, director of the UMG's Institute of Pathology and senior author of the publication.

After their discovery, the Göttingen scientists now want to research further links to metabolic processes that regulate the cellular stress balance in tumors.

In the future, a high-throughput screening will be carried out in cooperation with a pharmaceutical company in order to find new and even more effective substances with which angiosarcomas and other tumors can be combated.

Background information: Oxygen stress

Oxygen plays a vital role in many metabolic processes in cells. The use of oxygen can also jeopardize their function: Especially reactive oxygen molecules, so-called radicals, can damage the cell walls and the genetic material DNA and even destroy the cells.

Tumor cells suffer from high oxygen stress, but have found ways to deal with them. Tumors that are very successful here grow faster and are also less sensitive to chemotherapy.

Random observation

The Göttingen researchers made their observation by chance. Tumor cells grown from angiosarcoma patients did not all look the same under a microscope.

Most tumor cells were similar to normal vascular cells (more "cobblestone-like") and also mimicked vessels under special conditions. In addition, there were few cells that looked like “spindle-shaped” connective tissue cells and behaved much more aggressively.

The research team succeeded in isolating the two cell types and then investigating them more closely.

The Göttingen scientists have thus demonstrated for the first time that not all cells in angiosarcomas are identical: a small number of tumor cells lose certain important surface molecules that play an important role in the formation and function of blood vessels.

These few tumor cells lose the ability to form vascular structures and are therefore particularly aggressive.

Successful new therapeutic approaches

The researchers found that the loss of the surface molecule CD31 leads to the activation of a signaling pathway that not only makes the tumor cells significantly more aggressive, but also completely protects them from being destroyed by common chemotherapy.

"We were also able to regularly detect some tumor cells with low CD31 levels in tumor samples from patients with angiosarcomas," explained senior author Prof. Philipp Ströbel.

“We therefore believe that this is a generally important phenomenon that unfolds its full meaning when the patient has to be treated with chemotherapy or radiation. We are convinced that this small cell population in particular needs to be targeted for successful new therapeutic approaches. This strategy is very likely to be transferable to other tumors, ”said the expert. (ad)

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