KEY POINTS:
Scientists are developing a new weapon in the war on cancer by targeting the human genes that allow tumours to grow unchecked in the body.
Two separate teams of researchers have found a way of switching off critical genes within a tumour cell that would otherwise stimulate the
spread of the cancer.
Although the research is still at an early stage, scientists are describing the approach as potentially one of the most important developments since President Richard Nixon declared his "war on cancer" in 1971.
Doctors often describe cancer as a genetic disease because of the role played by genes in causing the uncontrolled proliferation of a cancerous cell into a tumour.
The radical approach is to use molecules of RNA - a substance similar to the DNA of the genes - to "silence" or switch off certain key genes known to be involved in the growth of tumours.
One team at the University of Oxford has shown in a laboratory study that it is possible to use large molecules of RNA to switch off a gene responsible for an enzyme called dihydrofolate reductase, which is essential for the rapid proliferation of tumour cells.
Another team, based in the German city of Tuebingen, has used smaller molecules of RNA in an animal study to switch off a separate gene known to be involved in the rapid growth of brain tumours.
Alexandre Akoulitchev, a senior research fellow at Oxford, said that there is a growing consensus among cancer workers that RNA molecules could generate new ways of treating the many different kinds of cancer that can affect the body.
"There's a quiet revolution taking place in biology during the past few years over the role of RNA," Dr Akoulitchev said.
The Oxford team has shown that it is possible to use RNA to directly affect the genetic "switch" controlling the gene for dihydrofolate reductase (DHFR).
When the DHFR gene is switched off, the rapidly dividing cancer cells are starved of a vital building block - a chemical called thymine.
"Inhibiting the DHFR gene could help to prevent the growth of neoplastic cancer cells - ordinary cells which develop into tumour cells - such as in prostate cancer cells," Dr Akoulitchev said.
"In fact, the first anti-cancer drug, Methotrexate, acts by binding and inhibiting the enzyme produced by this gene," he said.
The study is to be published in the journal Nature.
Another approach is being adopted by Professor Michael Weller, medical director of general neurology at the University Clinic in Tuebingen, who is using smaller molecules of RNA to silence a gene that would otherwise keep brain tumours from being attacked by the body's immune system.
In experiments on mice with malignant brain cancer all the tumours decomposed completely because they were no longer being protected by the silenced gene - known as TGF-beta.
"We saw the tumours grow, then we saw them regress.
I've been working on this for 10 years and it's the only technology where we've reliably produced cures for the animals," Professor Michael Weller said.
The research was carried out on gliomas, a highly malignant form of brain tumour.
About 30 per cent of patients with "primary" brain tumours that have arisen within the brain, rather than spreading there from cancers in other parts of the body, are gliomas.
A technique called RNA interference, which can "silence" a gene much like the dimmer switch of an electric light, was used to target TGF-beta gene within the cancer cells.
This gene sends out messenger molecules that protect the tumour against being attacked by the body's immune defences.
Once this block had been lifted, the immune defences were able to attack and eradicate the tumours.
Professor Weller found that the natural "killer" cells of the immune system were able to recognise and destroy the tumour, a feat that was bolstered by a vaccine made of dead tumour cells.
"These dead cells cannot proliferate any more. Therefore, they are not dangerous for the organism," Professor Weller said.
"These results could open the way for vaccinations against brain tumours, because only an immune system which is working faultlessly is able to react to a vaccination with an adequate immune response," he said.
"All the mice that received the RNA-interference therapy survived, yet all the animals that were not included died of their tumours. It was a black-and-white result.
"The results we achieved are indeed better than the results of using small molecules designed to perform the same task. It is difficult to explain why.
"The technology of RNA-interference is really a revolution in terms of being able to silence any type of gene in any type of disease," Professor Weller said.
The current trial was purely to see if RNA-interference could in theory be used to treat gliomas and further research is needed before human trials.
"At this time, such strategies are merely experimental as we did all our research on animals. These methods cannot yet be transferred to human patients," he said.
However, he expects that further developments could lead to the first clinical trials in two to five years time.
"I believe that gliomas will be one of the first diseases to be treated with RNA-interference," Professor Weller said.
The two American scientists who discovered RNA-interference, Andrew Fire and Craig Mello, won this year's Nobel Prize in medicine for their efforts.
- INDEPENDENT
