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The oncologist Clemens Schmitt of Kepler University Linz is developing a preventive dual therapy for cancer patients. The goal is to reduce the relapse rate.

Some patients defeat the cancer definitely, others suffer a relapse. Medicine is not yet able to prevent this. The causes for a relapse are manifold. Schmitt from the Department of Haematology and Internal Oncology researches suitable therapies. In January 2019, the oncologist moved from the Berlin Charité to the medical faculty of the Johannes Kepler University in Linz, which he has lead since then. His research focuses on the senescent cells that can trigger a relapse.

Elimination of Tumour Mass

In the first step, there is no room for alternatives in clinical cancer therapy. The aim is to eliminate the tumour mass. This is always the first goal, Schmitt says in an article in the current Kepler Tribune (2/19). Therapies such as surgery, chemotherapy or radiation are available. The aim is to kill as many tumour cells as possible. The normal tissue should not be significantly damaged.

Activation of Protection Mechanisms

Chemotherapy triggers programs in every tumour cell – apoptosis and senescence. These programmes are part of the body’s own protective mechanisms. They intervene when threatening changes occur in the body and eliminate the danger. If this does not happen, malignant cells can spread.

Cell Death

Apoptosis refers to programmed cell death and senescence to cell aging. The latter causes cells to no longer divide. Chemotherapy is used to stimulate apoptosis, cell death, in tumour cells. However, tumours change constantly – in their development and under therapy pressure. According to the oncologist, it is parts of this change that contribute to the resistance of individual cells to this killing mechanism.

Cell Aging

There are also tumour cells that are apoptosis-resistant and do not destroy themselves during chemotherapy. Alternatively, senescence, the self-aging of tumour cells, can be activated. This treatment has a tumour-controlling and thus life-prolonging effect on organisms affected by tumours. This has been confirmed.

Side Effect of Reprogramming

However, a therapy aimed at senescence raises new problems. Schmitt stated this in his latest study:

Senescent tumour cells spontaneously resume cell division on a case-by-case basis. If this happens, they are even more dangerous than tumour cells that were not in the senescence state. This is because the cells are massively reprogrammed epigenetically when they switch to senescence.

Among other things, the researchers discovered the activation of a stem cell programme. By dividing, the cells regain their stem cell capacity and induce a particularly aggressive relapse. In this case, a single cancer stem cell can produce a complete tumour.

New Therapeutic Window

Nevertheless, Schmitt continues to acknowledge the quality of the therapy aimed at senescence. With the help of senescence, a highly aggressive cancer can initially be limited. However, this is only a temporary solution, says the oncologist. He is now entering the next research phase and is trying to find methods to specifically attack the senescent cells. He is focusing on the reprogramming phase that the cell goes through when it switches to senescence. In this phase, many of the biological properties of the cells are altered, thereby creating new vulnerabilities. These have to be found, recognised and used in order to selectively switch off senescent cells. This is the approach that has established itself under the generic term senolysis.

The vulnerabilities of senescent cells offer a new therapeutic window. The data from the animal model were encouraging. Now the therapeutic potential of senolysisneeds to be clinically tested. This is the logical next step, explains Schmitt.

Reducing Relapse Rate

He now wants to test this double therapy – senolysisfollowing chemotherapy – in a clinical study. The aim is to significantly reduce the relapse rate. So far, one can only hope that there will be no relapse. Treatment will only be resumed once a clinically visible relapse has actually occurred.

If Schmitts’ study is successful and shows how to deal with the remaining tumour cells, it will take another decade before the method can be applied. Schmitt believes that studies will then be required in order to bring about a change of perspective in the clinical community.

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