Are cancer stem cells permanent
Achilles heel of tumors
For a long time it was thought that the cells within a tumor were all the same - now it is gradually becoming clear: the opposite is the case. Apparently most tumors have a hierarchical structure; a few cancer stem cells appear to be responsible for the growth, maintenance and metastasis of the tumor. This has not yet been clearly proven, but the results so far are already leading to a rethink in cancer research. Professor John Niederhuber, Director of the National Cancer Institute in the USA:
"There's growing evidence that this subset of cells exists. We've learned a lot about them in studying leukemia and lymphoma, and now we're making significant advances in solid tumors: colon cancer, breast cancer, lung cancer, and so on. But is it really crucial that we combat this subset of cells that have the ability to self-renew? The hypothesis is yes. So much depends on our better understanding of these cells and including them in cancer therapy. "
If chemotherapy and radiation are only aimed at normal cancer cells, as before, a tumor cannot be permanently defeated - even a single surviving tumor stem cell is enough to jeopardize healing, says Professor Andreas Trumpp from the German Cancer Research Center DKFZ in Heidelberg:
"The tumor is efficiently reduced by classic therapies, but the tumor stem cells, which are often just a few cells within the tumor, remain undetected in the body and can then be reactivated after a shorter or longer latency period Tumor comes back and it often comes back much more aggressively, metastasizes and then often leads to the death of the patient. "
Pancreatic tumors contain a particularly large number of the highly resistant stem cells; this is why this form of cancer is so difficult to treat. A research group at Heidelberg University Hospital recently succeeded in animal experiments to make therapy-resistant cancer stem cells sensitive to drugs again: with sulforaphane, an active ingredient in broccoli. Head of Studies Professor Ingrid Herr:
"We previously looked at the mechanism by which cancer stem cells protect themselves and we saw that a factor called NF-kappa-B transcription factor is over-activated in cancer stem cells. That's one reason these cells don't respond to chemotherapy. And we knew of the broccoli substance that it can inhibit NF-Kappa-B, and then also saw that programmed cell death was induced. "
It is possible that cancer stem cells can also be rendered harmless by making them mature into specialized cells - this is currently being investigated in brain tumors. Andreas Trumpp is pursuing another promising approach in the new Center for Stem Cell Research at the DKFZ: The tumor stem cells are often in a dormant state for years - because they hardly divide in this slumber mode, they also do not react to the common cancer drugs, which are always directed against active cells:
"We have identified certain proteins that cancel this dormant state, convert these stem cells back into an active state of division, making them sensitive to our classic chemotherapy, which in turn can kill dividing cells quite efficiently. That means first waking them up, then killing them."
Clinical studies with leukemia patients and breast cancer patients should soon show whether this approach also works safely in humans. Long-term success, however, will probably only bring a combination of different methods.
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