Apr. 15, 2005 Research into the development of cancer at the University of Liverpool could lead to earlier and improved detection methods for the disease.
University scientists have developed ways of detecting areas of instability in DNA that are known to lead to the development of cancer.
By applying this technology to early pre-cancerous lesions, they have made important discoveries on the timing of DNA damage and the response of cells to this damage.
Their research, funded by the Roy Castle Lung Cancer Foundation and published in this week's edition of Nature, demonstrates that breaks occur at fragile sites of cells' DNA very early in the carcinogenic process. The DNA breaks are produced by abnormalities in the cell division process that are caused carcinogens such as tobacco smoke.
This DNA damage occurs very early in the development of pre-cancerous cells and could highlight those at risk of developing cancer at a much earlier stage than current screening processes allow.
Dr Lakis Liloglou, Head of the University's Lung Cancer Molecular Biomarkers Group, explained: "These breaks occur preferentially in certain sites of the genome that are known to be fragile and induce a cell's pre-cancerous state. This initiates the cell's repair system, which fixes errors or leads damaged cells to die.
"If, however, the overall process fails because of an overload of an overload of carcinogens and the cell is not killed, this leads to multiplication of damaged cells which may develop in into a cancer. Identification of such damage could thus serve as a very early warning signal of cancer."
The team found that these mistakes (genomic instability at fragile sites) in the early stage of lung tumours and continuous exposure to carcinogens increase the chance that a precancerous lesion will progress to a cancerous one.
Dr Liloglou continued: "We have shown that early lesions that are virtually undetectable with current clinical methods carry molecular changes or mistakes that may commit cells to develop into a tumour."
"Our study emphasizes the need to develop molecular tests for detecting cancer at its pre-clinical stages, when chemoprevention regimes can be effective with minimal side effects for patients."
The study was carried out in collaboration with the Democritos National Centre of Scientific Research and the University of Athens Medical School in Greece, the Wistar Institute and the University of Pennsylvania in Philadelphia and the Mount Sinai School of Medicine in New York.
Professor John Field, Director of the Roy Castle Lung Cancer Research Programme at the University of Liverpool Cancer Research Centre, said: "This large international collaboration has identified one of the major mechanisms involved in the development of cancer, which will have enormous implications on our understanding of this devastating disease; in particular in lung cancer patients where early lesions are rarely identified prior to the diagnosis of the disease."
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