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Inhibition of the signaling pathways of cancer stem cells
A German research team discovered a new method that can block the growth of tumors in the kidney. The team deciphered a dangerous cancer stem cell that is responsible for the most common type of kidney cancer.
Researchers at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, together with the Department of Urology at the Charité Berlin, discovered a specific type of cancer stem cell that causes kidney cancer particularly often. The team also developed a therapy to block the growth of these tumors. The results were recently presented in the renowned journal "Nature Communications".
Cancer stem cells are of particular importance
Not every cancer cell is the same. Some stem cells within tumors are particularly dangerous because they create metastases that cause cancer to develop again. For this reason, cancer stem cells are of particular interest in cancer research. However, these cells are so rare and so difficult to find that they have not been discovered in most cancers. The team led by Walter Birchmeier has now made this discovery in so-called clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer.
The weakness of the cancer stem cell
The researchers also identified a weak point in the cancer stem cells. Because the cells are dependent on two essential biochemical signals. When the team blocked both signals, tumor growth stopped in several laboratory models. According to the research team, this represents a promising approach to treating kidney cancer.
Only two percent of cancer cells are stem cells
Initially, the scientists were able to identify three proteins on the cell surface of the cancer stem cells, which allowed them to mark and isolate them in subsequent steps. The team discovered that only around two percent of the cells in human tumors are cancer stem cells.
Disrupt the communication of tumor cells
"Our analysis of these cells shows that they depend on signals that are transmitted through two biochemical networks called WNT and NOTCH," reports lead author Dr. Annika Fendler. Since these networks are also important for other types of cancer, ways were known to interrupt the WNT signals with an inhibitor.
Inhibitors can replace chemotherapy
Such inhibitors, which are also called inhibitors of biochemical signaling pathways, are increasingly replacing chemotherapy in the treatment of cancer. "However, you always have to know which signal path to aim at," emphasizes Fendler. Current research shows for the first time such an approach in kidney tumors.
A new animal model
Birchmeier's team managed to transplant cancer stem cells from human patients into mice. The tumors that subsequently developed were practically identical to human kidney carcinomas. According to the researchers, these animals are central to the search for therapies. Because what heals human tumors in mice can also work in humans.
Artificially grown tumors
Another new model is the production of so-called organoids. These are miniature versions of organs grown in the laboratory. "Although they are made of human tissue, they can be used without the ethical problems that arise when testing agents on patients," the researchers explain. Such organoids have already been grown for healthy kidneys, as well as for various other organs and for tumors such as colon cancer.
New bespoke approaches to cancer
In all models used, the blocking of the signaling pathways had an impact on tumor growth. "The most important result of the study is that we have identified the essential roles of the WNT and NOTCH signaling systems in ccRCC and that we show that their blocking has an impact on the tumors," Birchmeier sums up. The researchers hope that the approach developed in the models will make the leap to the clinic and ultimately lead to tailor-made therapies for kidney cancer. (vb)
Author and source information
This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Graduate editor (FH) Volker Blasek
- Max Delbrück Center for Molecular Medicine: Cutting off kidney cancer at its roots (published: February 17th, 2020), mdc-berlin.de
- Fendler, Annika et al .: Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients; in: Nature Communications, 2020, nature.com