Finding cures for children's genetic diseases

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Commentary: New ALT research tool found

12/Jan/2014   By: Professor Roger Reddel




An almost universal feature of cancers is that their cells acquire the ability to proliferate without limit. Some cancers achieve this via a process termed ALT (Alternative Lengthening of Telomeres), and the cancers that commonly use ALT include some of the most aggressive brain cancers and sarcomas.

An attractive strategy for treating these types of cancers is to find drugs that interfere with ALT. But in order to do this, we need to understand the molecular details of ALT and also how cancer cells are able to switch this process on.

What Dr. Karlseder and his team report in this paper is that they have figured out, for the first time, how to switch ALT on rapidly in cells growing in the laboratory. This is a major achievement which will help speed up this area of cancer research.

What they have discovered is a genetic manipulation that causes the tell-tale signs of ALT activity. It didn't work in all of the types of cells that they tried, but in the cells where it did work, it happened fast (within about three days) and appeared to be reliable. There were also some intriguing hints that ALT activity continued even when the genetic manipulation was reversed, suggesting that ALT activity results in a vicious cycle:  it changes the cells in a lasting way so that ALT will keep on happening.

The authors of this paper think that the genetic manipulation they discovered is most likely different from the genetic changes which are actually responsible for switching ALT on in cancers. They therefore describe it as a very useful laboratory "tool" for studying ALT.

And in a demonstration of how useful this laboratory tool is, they also report its use to pinpoint some of the molecules involved in unleashing ALT. Drugs that interfere with these molecules may be prime candidates for treating some of the cancers that depend on ALT for their continuous growth and aggressive behavior.