An international study published in Nature today has identified a previously unknown faulty gene that appears to play a key role in aggressive forms of pancreatic cancer.
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.
Dr Stephen Wood, Research Member from Griffith’s Eskitis Institute for Cell and Molecular Therapies, one of the lead investigators said the study based on mouse model results looked at 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 (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.
“Several other pancreatic tumour suppressor genes are known to exist, but this is the one whose absence probably promotes metastasis, and that is what kills people with pancreatic cancer,” said Dr Wood.
“Our observation has two major implications. First it allows us to potentially treat people that have lost this gene expression in the pancreatic tumours. It allows us to offer a therapy for the patients that actually have the worst prognosis. Second, it will help us identify novel avenues in preventing pancreatic cancer.”
Dr Wood says drugs which re-activate gene expression have already been developed but people haven’t figured out where exactly they would be useful.
“We are proposing that these drugs could be useful in this subset of pancreas cancer patients.”
Pancreatic cancer kills about 96 percent of its victims within five years of diagnosis, one of the lowest cancer survival rates.
Early diagnosis is difficult, so the disease is often discovered only after it has already spread.
This study involved an international collaboration of labs from all over the globe, each with a unique contribution to make.
Dr Wood emphasised that this major breakthrough in cancer research could only come about by the collaboration of pancreatic cancer specialists, clinicians, people working with mouse models and our knowledge of the biology of USP9X.