Medicine: Dark side of drug cancer therapy

Medicine: Dark side of drug cancer therapy

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Researchers looked at the dark side of drug cancer treatment

More and more people are getting cancer. In many cases, the serious illness is also combated with medication. German researchers have now dealt with the dark side of drug therapy for cancer.

The number of new cancer cases has almost doubled since 1970

According to the World Cancer Report of the International Agency for Research on Cancer (IARC), 20 million new cases of cancer could occur each year by 2025. More and more people are affected in this country too. The number of new cases in Germany has almost doubled since 1970. In many cases, those affected are treated with medication. Scientists from Charité - Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine (MDC) have dealt with the dark side of this therapy and have now published their results in the journal "Nature".

Prevent tumor cells from growing further

If malignant changes are imminent in the cells of our body, built-in self-protection programs intervene and often prevent cancer.

Two of these tumor suppressor mechanisms are programmed cell death, called apoptosis, and the acute triggering of a cell aging program, the so-called senescence. The mechanisms prevent cell division and tumor growth.

These programs are also activated during chemotherapy and convey the anti-tumor effect.

The team around Prof. Dr. Clemens A. Schmitt, director of the Charité Molecular Cancer Research Center and researchers at the MDC and the German Consortium for Translational Cancer Research (DKTK) were able to show a few years ago that switching on cellular senescence is an important and desirable factor, especially in the case of tumor cells that are often defective in apoptosis Therapy effect is to prevent the tumor cells from further growth.

Particularly threatening ability of tumor cells

In their new study, the research team observed that the growth-blocked tumor cells undergo massive epigenetic reprogramming when they enter senescence.

This results in a new coding of various cellular work programs, including the activation of a stem cell program, also referred to as “tumor stemness”.

Tumor stemness describes the particularly threatening ability of tumor cells to drive or even start tumor growth, as is the case, for example, with the development of daughter tumors.

Since stem cell function is necessarily linked to cell division, the cancer researchers examined whether switching off individual genes that are absolutely necessary for maintaining senescence could make the newly acquired stem cell capacity of the previously senescent cells functionally visible.

In fact, the formerly senescent tumor cells behaved much more aggressively than the same tumor cells that had never entered the senescence state.

Study results provide insight into the skillful behavior of the tumor cells

Investigations in in vivo tumor models confirmed the relevance of these cell culture findings.

Using a new single cell tracking technique, the scientists were also able to show that senescent tumor cells can rarely spontaneously re-enter the cell division cycle.

A comparison of tumor samples in lymph gland cancer before the start of therapy and later in the relapse of the same patients suggested that such previously senescent cells after chemotherapy contribute to the particularly aggressive tumor growth in treatment failure.

"These results are very important clinically because they give us insight into the skillful behavior of the tumor cells to prevail against actually very effective cancer treatments," explains Prof. Schmitt.

"Fortunately, in this research we were also able to present genetic and drug strategies that directly attack and neutralize the newly acquired tumor stemness of previously senescent tumor cells," he adds.

In subsequent experiments and a currently planned clinical study, the scientists led by Prof. Schmitt, who as a lymphoma specialist treats patients with lymphoma cancer in the Charité on a daily basis, will continue to investigate the role of senescence-associated stem cell reprogramming in lymphoma patients targeted approach to therapy. (ad)

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