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 the former US president Richard Nixon declared his "war in 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 a gene's DNA - 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 (DHFR), which is essential for the rapid proliferation of tumour cells.
Another team, based in the German city of Tübingen 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 scientists that RNA molecules could generate new ways of treating the many different kinds of cancer that can affect the body. "There has been a quiet revolution taking place in biology during the past few years over the role of RNA," he said.
The Oxford team has shown that it is possible to use RNA to directly affect the genetic "switch" controlling the gene for DHFR. When it is switched off, the rapidly dividing cancer cells are starved of a vital building block - a chemical ca
lled 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 Oxford 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 Tübingen, who is using smaller molecules of RNA to silence a gene that otherwise protects 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 Weller said.
The two American scientists who discovered RNA-interference, Andrew Fire, of Stanford University, and Craig Mello, from the University of Massachusetts, won last year's Nobel Prize in medicine.
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