News Editor, Sydney
The discovery of a tumour suppressing gene could offer hope to patients with the deadliest form of cancer, new research has shown.
An international team of researchers, including scientists from Australia, has been able to identify a faulty gene that is instrumental in the most aggressive forms of pancreatic cancer, which kills more than 600,000 people each year.
The research is reported in the latest online edition of the journal Nature.
The gene, called USP9x, could effectively “go missing” in around one in seven pancreatic cancers, the team found. Research on human cell lines and mice demonstrated that the gene is switched off by chemical tags on the surface of its DNA.
After discovering the gene, dubbed USP9X, in a study of pancreatic cancer in mice, the international research team went on to show that it plays a similar role in humans.
Stephen Wood, Research Member from Griffith’s Eskitis Institute for Cell and Molecular Therapies and one of the lead researchers, said that “based on the mouse model results, we looked in human tumour specimens and found that it was missing in a significant fraction of patients – those who died the fastest.
“Although there are no mutations in the USP9X gene, patients that had a low level of gene expression died very quickly after their operation. In addition, patients who at the end of their life had many metastases – or spreading of the cancer – also had a very low level of this protein. In this study we identify chemicals which can re-activate USP9X gene expression.
“My group has worked on USP9X for several years and shown it is expressed in many of our cells. This collaborative study is the first to show that it goes missing in some tumours, and it has a novel role as a cancer suppressor."
Dr Wood said that several other pancreatic tumour suppressor genes were known to exist, but that USP9X was the one whose absence probably promoted metastasis, “and that is what kills people with pancreatic cancer”.
The finding had two major implications, he said. It allowed scientists to potentially treat people who had lost this gene expression in their pancreatic tumours. And it could help identify novel avenues in preventing pancreatic cancer.
Dr Wood said drugs that re-activated gene expression had already been developed. But scientists had not yet determined where exactly they would be useful.
Pancreatic cancer kills about 96% of its victims within five years of diagnosis, which means it has one of the lowest cancer survival rates.
Early diagnosis is difficult, so the disease is often discovered only after it has already spread.
Lead scientist Professor David Tuveson, from Cancer Research UK’s Cambridge Research Institute, said: “Drugs which strip away these tags are already showing promise in lung cancer and this study suggests they could also be effective in treating up to 15% of pancreatic cancers.”
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