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Cancer cell "executioner" found--BBC
Cancer cell 'executioner' found
Cancer cells keep dividing because the cell suicide process fails
Scientists have developed a way of "executing" cancer cells.
Healthy cells have a built-in process which means they commit suicide if something is wrong, a process which fails in cancer cells.
The University of Illinois team created a synthetic molecule which caused cancer cells to self-destruct.
Cancer experts said the study, in Nature Chemical Biology, offered "exciting possibilities" for new ways of treating the disease.
These findings present an exciting new therapeutic strategy for the treatment of some cancers
Dr Michael Olsen, Cancer Research UK
One of the hallmarks of cancer cells is their resistance to the body's cell suicide signals, which allow them to survive and develop into tumours.
All cells contain a protein called procaspase-3, which the body should be able to turn into caspase-3 - an executioner enzyme.
But this transformation does not happen in cancer cells, even though certain types, such as colon cancer, leukaemia, skin and liver cancers paradoxically have very high levels of procaspase-3.
Healthy cells unaffected
The researchers examined more than 20,000 structurally different synthetic compounds to see if any could trigger procaspase-3 to develop into caspase-3.
They found the molecule PAC-1 did trigger the transformation, and cancer cells from mice and from human tumours could be prompted to self-destruct - a process called apoptosis.
The more procaspase-3 a cancer cell had, the less of the molecule was needed.
Healthy cells, such as white blood cells, were found to be significantly less affected by the addition of PAC-1 because they had much lower levels of procaspase-3, so cell-suicide could not be triggered.
When the scientists tested PAC-1 on cancerous and non-cancerous tissue from the same person, the tumour cells were 2,000-fold more sensitive to PAC-1.
Since different levels of procaspase-3 were found in the cell lines studied, the researchers suggest some patients would be more responsive to this therapy than others, so the it might one day be possible to tailor treatments to individual patients.
'Exciting'
Professor Paul Hergenrother, who led the research, said: "This is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes.
"The potential effectiveness of compounds such as PAC-1 could be predicted in advance, and patients could be selected for treatment based on the amount of procaspase-3 found in their tumour cells."
Cancer Research UK expert Dr Michael Olson, who is based at the Beatson Institute for Cancer Research in Glasgow, said: "These findings present an exciting new therapeutic strategy for the treatment of some cancers.
"It remains to be seen which, if any tumour types consistently express elevated procaspase-3. That will tell us how many patients could potentially benefit from the drug.
"Clinical trials will be needed to confirm whether procaspase-3 causes any adverse effects in humans."
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