Scientists out cancer cells in permanent coma

Mar 29 2005

Scientists funded by Marie Curie Cancer Care and the Association for International Cancer Research have made an unexpected discovery that could point the way to a completely new approach to treating cancer.

Current treatments are based on cutting out or killing cancer cells. Now scientists based at the Marie Curie Research Institute, in Surrey, believe the work could lead to a third way of dealing with them. They have successfully put cancer cells into a permanent ‘coma’ by reactivating a natural self-defence mechanism which responds to dangerous mutations by putting the cell into a state called senescence – meaning that it cannot divide any more.

In cancers this safeguarding mechanism is bypassed, enabling cell division to run out of control. Scientists previously thought that in cancers it was damaged beyond repair.

This new work published on the 15th March 2005 [1] shows that they can switch back on the mechanism that triggers senescence in cells for the deadly skin cancer malignant melanoma. The cells stop dividing – and never divide again.

Dr Colin Goding, Head of the Signalling and Development Group, who led the research, explained: “When certain genes called oncogenes are activated by mutation, they cause cancer to develop. Many oncogenes control cell growth or cell division.

“When these are mutated, it’s like the accelerator in a car being jammed on – the cell is continuously getting instructions to divide: “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 will 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.

“We were looking at a gene called Tbx2, which is too active in melanoma and other cancers, and wanted to know exactly what it did and how it did it. It turned out to be linked to a mechanism that repressed senescence.

“What really surprised us was that when we inhibited Tbx2 in melanoma cells, they senesced and stopped dividing. This means we have potentially a new way of stopping cancer cells dividing.

“Now we want to find out in what proportion of melanomas and other cancers we can induce senescence. We are not sure whether this will be effective against all melanomas or just some.

“Being able to design drugs that reactivate senescence would be a great boon. The beauty of it is that this natural mechanism would automatically target cells which have the accelerator jammed on – it would hit the cancer cells, but not normal cells.” he added.

The work of Dr Goding’s team is funded in part by the Association for International Cancer Research. Chief Executive, Derek Napier believes the research could open up a whole new approach to treating cancer in the future.

He said: “Malignant melanoma is a particularly fast growing cancer and we don't have any really effective treatments for advanced cases. This work will excite the scientific community because of the possibility that this protective self-defence mechanism could form the basis of a potential treatment, not only for melanomas but also for other fast-growing cancers like breast, prostate and pancreatic cancer, which between them kill more than 30,000 people in the UK every year – almost 3,000 of them in Scotland.”