Cancer Research UK-funded scientists have shown how a promising new class of drugs might be used to treat aggressive forms of pancreatic cancer, according to a study published in Nature.
Pancreatic cancer kills around 8,000 people every year and, although survival rates are gradually improving, fewer than one in five patients survive their disease for a year or more.
Scientists from Cancer Research UK’s Cambridge Research Institute and the Wellcome Trust Sanger Institute showed, in human cancer cells and mice, that a gene called USP9x is switched off through chemical tags on the DNA’s surface.
They believe the gene could be involved in up to 15 per cent of pancreatic cancers, raising the prospect that existing drugs, which strip away these chemical tags, could be an effective way of treating some pancreatic cancers.
It may also explain why the gene has not been identified through studies involving traditional gene-hunting approaches, which only detect changes in the sequence of the DNA.
Co-lead author Professor David Tuveson, from Cancer Research UK’s Cambridge Research Institute, said: “The genetics of pancreatic cancer has already been studied in some detail, so we were surprised to find that this gene hadn’t been picked up before. We suspected that the fault wasn’t in the genetic code at all, but in the chemical tags on the surface of the DNA that switch genes on and off, and by running more lab tests we were able to confirm this.
“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 per cent of pancreatic cancers.”
The researchers used a mouse model of pancreatic cancer to screen for genes that speed up pancreatic cancer growth using a technique called the ‘sleeping beauty transposon system’. A transposon is a piece of DNA that can spontaneously hop around the cell’s DNA from one location to the next, often landing right in the middle of a gene and stopping it from working.
By introducing the sleeping beauty transposon into mice with pancreatic cancer, the researchers were able to screen for ‘tumour suppressor’ genes that, under normal circumstances, would protect against cancer. These genes are a bit like the cell’s ‘brakes’, so when they become faulty there is nothing to stop the cell from multiplying out of control.
This approach uncovered many genes already linked to pancreatic cancer. But unexpectedly, the most common gene fault was one with no previous links to any cancer type.
Co-lead author Dr David Adams, from the Wellcome Trust Sanger Institute, said: “The human genome sequence has delivered many new promising leads and transformed our understanding of cancer. Without it, we would have only a small, shattered glimpse into the causes of this disease. This study strengthens our emerging understanding that we must also look into the biology of cells to identify all the genes that play a role in cancer.”
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “These results raise the possibility that a class of promising new cancer drugs may be effective at treating some pancreatic cancers.
“Fewer than 20 per cent of people survive pancreatic cancer for a year after diagnosis – a situation that has improved little in the last 20 years. Studies like this one are part of Cancer Research UK’s commitment to invest more in hard-to-treat cancers like pancreatic cancer, hopefully improving treatment to save more lives in the future.”
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- Pérez-Mancera, P et al (2012). The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma Nature DOI: 10.1038/nature11114