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Far-reaching effects
This research, however, has potential significance far beyond this particular condition. There are undoubtedly other cancers whose cause or progression would be modulated by the same pathway, says Keith Wilkinson, professor of biochemistry at Emory University in Atlanta. Wilkinson wrote a commentary accompanying the articles, which appear in the Aug. 14 issue of Nature.
In addition to identifying the mechanism at work, the researchers have also discovered that plain old aspirin may have a salutary effect.
A gene called CYLD
Researchers had already identified a gene called CYLD which, when mutated, leads to the development of these specific tumours. Until now, however, no one knew exactly how the gene worked.
The Nature researchers found that CYLD controls a protein that, under normal circumstances, is only turned on temporarily in response to an injury or another event. Scientists believe that tumours develop when the protein is turned off and loses its function.
Normally when something is turned on, there is an innate mechanism to turn it off, says David Wallach, senior author of one of the studies and a professor at the Weizmann Institute of Science in Rehovot, Israel. Andrew Kovalenko, also of the Weizmann Institute, was the lead author of that study. A fine tuning exists in all signalling. After being activated, then something is activated to stop it.
When the protein is working properly, it temporarily stimulates the activity of a pathway inside the cell called NF-kappaB. Normally, this pathway prevents apoptosis, or normal cell death, among other things.
When we have an elevated activity of this pathway, the cell refuses to die, says George Mosialos, senior author of one of the studies and group leader at the Alexander Fleming Biomedical Sciences Research Center in Vari, Greece. What we think is happening in these tumours, because they cannot die easily, they lead to development of tumour mass.
The discovery of an important mechanism
The essence of the new finding is the discovery of an important mechanism of negative feedback in the activation of NF-kappaB, Wallach says.
The same mechanism could be at work in other types of tumours. The elevated activity of this pathway is a common mechanism for a number of other tumours, namely leukaemias and lymphomas, so by understanding another regulatory mechanism of this pathway, we feel that we can probably contribute also in the understanding of other types of tumours, Mosialos says.
Anti-inflammatories might restore the balance
The other potentially exciting news is that anti-inflammatory agents such as aspirin and prostaglandin A1 might inhibit that pathway and restore balance.
But that theory comes with several caveats. We have to understand that these are not very efficient inhibitors of the pathways, so in order to have an effect we may have to use large amounts of aspirin, Mosialos says. We have to find more efficient inhibitors of the pathway, and we think that such inhibitors would be beneficial to these tumours.
It's possible that, in very defined cases, anti-inflammatories could be helpful, but that's certainly not been demonstrated, Wilkinson adds. It's a very suggestive idea that that might be a pathway that we could develop drugs against, that in certain cases would be helpful. But it's a long, long way from a treatment at this moment. - (HealthDayNews)
