Breakthrough over cancer protein
Updated on 21 January 2009
The first "working" model of a key cancer protein has exposed an Achilles heel which could pave the way to wide-ranging new treatments.
British scientists created the moving interactive model of the enzyme protein kinase B (PKB) to see how it functions in cells.
PKB is an important regulator of signalling pathways that control cell survival and proliferation. Excessive activation of the molecule is one of the major driving forces behind cancer and seen in many tumours.
Currently there are no drugs suitable for use in humans that can switch off out-of-control PKB. But the model exposed a hidden "cavity" in the protein's structure which is crucial to regulating its activity. The scientists found that inhibitor molecules can bind to the cavity area and lock PKB into an inactive state.
Research leader Professor Banafshe Larijani, head of the Bell Biophysics Laboratory at the charity Cancer Research UK's London Research Institute, said: "An overactive form of PKB is observed in tumours, so finding a way to switch this enzyme off lets us, in effect, put up road blocks along routes by which cancer can develop.
"Our team has deduced for the first time the model structure of this critical protein and how it interacts with other molecules in the cell. This means we now understand how existing drugs keep it in check, giving us the information we need to develop better ones."
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "We have recognised the important role this protein can have in driving cancer development and now we know its full structure, the coast is clear to develop new therapies which will help in our fight to beat cancer."
Experts already knew that some "allosteric" drugs which cause proteins to change shape and alter function can turn off PKB, but they are not safe for humans.
Previously no-one understood how these drugs interacted with PKB. Now the mechanism is known, scientists hope new drugs can be developed that can safely be given to cancer patients. Since PKB affects the growth of many kinds of tumour, it could lead to the development of the first "broad spectrum" cancer treatment.
The research is published in the online journal PLoS Biology
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