Cancer: Improved Effectiveness of Chemotherapy

Photo: Tumor cell

So-called "mitotic catastrophe" of a tumour cell: The image shows that the tumour cell is no longer able to divide after chemotherapy; © University of Bern/Hans-Uwe Simon

Cancer cells often develop defense mechanisms to survive chemotherapy. A group of researchers from the Institutes of Pharmacology and Pathology in Bern present new solutions for preventing the development of such resistances.

Cells can break down damaged molecules as well as whole areas of the cells themselves by means of self-digestion and utilize the decomposition products resulting from this process for the production of energy and new molecules or cell parts. This process of self-digestion is called autophagy and can be considered a renovation of the cell. The generation of energy by means of autophagy plays a special role for the cells if they do not have enough nutrients, oxygen or growth factors.

However, autophagy can also be used by tumor cells in order to survive stress situations such as chemotherapy - they digest the destroyed cell parts and regenerate themselves. This makes them resistant to the therapy. Now, a group of scientists from the University of Bern under the direction of Hans-Uwe Simon from the Institute of Pharmacology has discovered that the autophagy of tumor cells can be influenced with pharmacological means. The findings reveal new therapy approaches for the treatment of cancer.

The researchers studied the importance of autophagy for tumor cells. Often, chemotherapy alone is not able to destroy all of the tumor cells. While some of the tumor cells survive the therapy by means of autophagy, others go through a so-called “mitotic catastrophe”, a state in which they are no longer able to divide. If these damaged cells do not die, they can cause cancer again.

Now, however, the group of scientists gathered by Simon has found a way to prevent the survival of cancer cells after chemotherapy. They discovered a connection between autophagy and mitotic catastrophe: when the self-digestion of cancer cells was suppressed by means of pharmaceuticals, the mitotic catastrophe directly resulted in cell death. This way, the survival mechanisms of cancer cells were eliminated.

With this method, the effectiveness of the usual chemotherapy can be significantly improved: "We hope that, based on these findings, we will be able to develop new therapies which will prevent the chemoresistance of established tumours", Simon said.; Source: University of Bern