Cancer Breakthrough as Tumour Cells Sent to Sleep
Published: March 15, 2005
Pioneering research by British scientists has found a new way of fighting cancer by sending tumour cells to sleep, it was revealed today.
Experiments with skin cancer cells show they can be frozen into a permanent state of suspended animation which stops them multiplying.
Although the cells do not die, the uncontrolled cell division characteristic of cancer is halted.
The coma-like effect, known as senescence, is a natural defence the body uses to prevent damaged cells triggering cancers.
When the mechanism breaks down, rogue cells are left to multiply and spreading cancer can result.
Scientists around the world have investigated senescence, but the British team is believed to be the first to show it can be re-activated once disabled.
They hope the discovery will lead to new treatments for malignant melanoma, the deadliest form of skin cancer, and possibly other cancers.
Dr Colin Goding, who led scientists from the Marie Curie Research Institute in Oxted, Surrey, said: “The fact that over 150,000 people die from cancer in Britain each year suggests that we need a different way to tackle the disease.
“At present, most therapies rely on killing cancer cells or apoptosis, programmed cell-death.
“This looks great to me. For the first time I think we’ve got something that really has the potential to make a difference.”
Cancers are often triggered by defective genes involved in the control of cell growth or division.
When these oncogenes mutate, it is like an accelerator in a car being jammed on, said Dr Goding. The cell is continuously receiving instructions to divide.
Dr Goding said: “In our lifetime of 70 years or so, we get mutations in these genes all the time, but may only get cancer once. That is partly because we are protected by the senescence mechanism.
“Normal cells sense that something is wrong – that the accelerator is jammed on – and they put on this brake on cell division called senescence, which means the cell can never divide again. It’s in a coma – permanently.
“We thought that when normal cells became melanomas, it wasn’t possible to switch on senescence – these are cancer cells, so by definition, they’ve overcome this braking mechanism.”
But the researchers were surprised to find that when a gene called Tbx2 was inhibited in proliferating melanoma cells, it switched on senescence.
“This means we have potentially a new way of stopping cells dividing,” said Dr Goding.
Tbx2 is overactive not only in melanoma but also some other cancers, including certain breast cancers.
Last year Dr Goding’s team published research showing that Tbx2 regulated another gene called P21, which is known to be involved in senescence.
“We put two and two together and asked: ‘Is it possible that Tbx2 acts to suppress senescence in melanoma?”’ said Dr Goding.
Working in the laboratory, the scientists genetically modified Tbx2 in melanoma cells taken from both mice and humans.
This had the effect of making the gene less active, and removing the block on senescence.
But much more work must be done before the first patients can be treated.
Scientists will first have to identify which cancers will respond to the treatment and which will not.
A gene-therapy approach is also not practical as a clinical treatment. Instead drugs will have to be found that have the same effect of inhibiting Tbx2.
Dr Goding did not expect to see clinical trials for another 10 years.
Nonetheless the findings, published today in the journal Cancer Research, are seen as a major step forward.
Skin cancer specialist Dr Tim Eisen, from the Royal Marsden Hospital, London, said: “At present we do not have very effective treatment for melanoma once it has spread to other parts of the body. Dr Colin Goding’s discovery is an important contribution to this exciting field. It suggests new ways of tackling melanoma – although much work remains to be done.”
The Marie Curie Research Institute is part of Marie Curie Cancer Care, a national charity which provides home nursing for terminally-ill cancer patients and runs 10 hospices across the UK.
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