June 16, 2010 The new cancer medication sorafenib looks promising. Sorafenib is used for advanced liver and kidney cancer and also appears to be effective against cancer stem cells in pancreatic cancer. A team led by Professor Dr. Ingrid Herr, Head of the Department of Molecular Oncosurgery, a group of the Department of Surgery at Heidelberg University Hospital, (Managing Director: Professor Dr. Markus W. Büchler) in cooperation with the German Cancer Research Center, tested the new substance in mice and pancreatic cancer cells. It inhibits resistant tumor stem cells and is also especially effective in combination with sulforaphane, an organic compound found in broccoli.
The results has been published online in the medical journal Cancer Research.
About 12,900 people in Germany develop pancreatic cancer every year. The disease is frequently noticed too late and very few people survive the diagnosis longer than one year. In particular, early precursor cells of the tumor known as cancer stem cells are responsible for uncontrollable growth of the cancer, metastasization to other organs, and recurrence shortly after surgery. They are extremely resistant to conventional therapy and are the focus of new treatment strategies.
Sorafenib is also effective for pancreatic cancer
In their tests on cancer cells and mice, the researchers showed that sorafenib inhibited typical properties of cancer stem cells from pancreas tumors and greatly reduced tumor growth. However, this effect lasted only for a short time and after four weeks, new colonies of cancer stem cells formed that no longer reacted to further treatment with sorafenib. "This resistance is probably related to a certain metabolic pathway, the NF-kB pathway, that is activated by sorafenib," explained Vanessa Rausch, a young researcher at the department of Surgery at Heidelberg University Hospital and first author of the article.
Broccoli reinforces the effect of sorafenib
There are naturally occurring substances that block precisely this undesired NF-KB pathway and thus make the dangerous cells vulnerable: vegetables from the cruciferous family such as broccoli and cauliflower possess a high content of sulforaphane, an anti-cancer compound. The experiments show that sulforaphane prevents the activation of the NF-kB pathway by sorafenib. The combination treatment reinforces the effect of sorafenib without causing additional side effects. The invasive potential of cancer cells was prevented -- metastasis was completely blocked in cell culture experiments. "We assume that nutrition may be a suited approach to break therapy resistance of cancer stem cells and thus make tumor treatment more effective," Professor Herr suggested.
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- V. Rausch, L. Liu, G. Kallifatidis, B. Baumann, J. Mattern, J. Gladkich, T. Wirth, P. Schemmer, M. W. Buchler, M. Zoller, A. V. Salnikov, I. Herr. Synergistic Activity of Sorafenib and Sulforaphane Abolishes Pancreatic Cancer Stem Cell Characteristics. Cancer Research, 2010; 70 (12): 5004 DOI: 10.1158/0008-5472.CAN-10-0066
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