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Reason for high colorectal cancer relapse rates discovered

Reason for high colorectal cancer relapse rates discovered


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Why common cancer drugs promote colorectal cancer relapse

A certain group of cancer drugs apparently leads to increased colon cancer relapse rates. A German research team recently discovered in a study that common active substances to fight colon cancer initially kill the cancer cells, but at the same time also stimulate the stem cells to develop new and more resistant cancer cells.

Researchers at the German Cancer Research Center (DKFZ) decoded a process that appears to be responsible for an increased relapse rate in colorectal cancer. The research team discovered that a group of cancer drugs in colon cancer cells activate the so-called Wnt signaling pathway. This signal path promotes the accumulation of resistant tumor cells, which can then lead to a severe relapse after successful therapy. The study results were recently presented in the renowned journal "nature communications".

New function of the Wnt signal paths discovered

Wnt signaling is a biochemical reaction of cells to external influences. They already coordinate the development of embryos, but also play a role in many disease processes. For many years, doctors have believed that overly activated Wnt signaling pathways are linked to the development of cancer. So-called MEK inhibitors are used to throttle these overactive signaling pathways. However, the latest research shows that this influence can lead to resistant cancer cells accumulating in stem cells. If there is a relapse, many therapies have no effect.

Colon cancer cells can change their state via Wnt signals

"Wnt signals have an effect on the balance between cells with stem cell properties and differentiated cells, both in the healthy intestine and in colon cancer," explains Michael Boutros in a press release from the DKFZ. This signaling pathway is particularly active in colorectal cancer stem cells and is responsible for maintaining the stem cell properties. This means that cancer cells can switch back and forth between a stem cell state and a “normal state”. The normal cancer cells can usually be killed by medication, but the stem cells survive and pose a risk of relapse as "sleeping cancer stem cells".

MEK inhibitors promote cancer stem cell growth

The growth of many tumors is promoted by so-called Ras signaling pathways. To inhibit these signaling pathways, doctors use drugs with MEK inhibitors. Although the division rate of colorectal cancer cells can be reduced, the current study shows that cancer stem cells accumulate at the same time. The researchers demonstrated this both on mice and on colon cancer cells grown in the laboratory.

The principle of sleeping cancer stem cells has been deciphered

This knowledge plays a crucial role in the success of treatment for colorectal cancer. "This corresponds exactly to the picture of sleeping cancer stem cells, which have been described in many types of cancer for several years," emphasizes student author Tianzuo Zhan. Because exactly these cells are responsible for relapse because they survive the therapy. The DKFZ research team now wants to find a way to block the influence of MEK inhibitors on Wnt activity in order to make colon cancer therapy more successful. (vb)

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