Discovery offers new target in pancreatic cancer treatment
6 January 2013Researchers at the Mayo Clinic in Florida have identified a potential way to improve treatment of the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma, which accounts for more than 95 per cent of pancreatic cancer cases.
Published in the journal PLOS ONE, the study has made sense of a specific complex sequence of interactions between genes and proteins (known as a molecular pathway) that has become permanently ‘switched on’ in pancreatic cancer, promoting accelerated tumour growth.
The team believes that their findings offer a potential new target for drugs to help subdue or block the pathway, and suggest that treatment could involve the use of the drug bortezomib, which is already approved for use in treating several human blood cancers.
A key feature of pancreatic cancer is increased activity of a protein called NF-kB, which is known to play a role in switching on genes that keep cancer cells growing unchecked. There are two pathways by which NF-kB can be activated, known as the classical pathway and the alternative pathway. Although both of these are active in pancreatic cancer, they work in different ways.
When the researchers examined the NF-kB alternative pathway, they found that the increased activity of NF-kB was caused by the normal defences – a protein known as TRAF2 which protects cells from unregulated growth, being suppressed. They also found higher levels of other molecules becoming involved in the alternative pathway.
They tested this discovery in 55 human samples of pancreatic cancer and found that in over two thirds of these, the protective protein TRAF2 wasn’t working properly.
Loss of TRAF2 promotes fast growth of pancreatic tumours and correlates with increased aggressiveness, said study leader Dr Peter Storz, a biochemist and molecular biologist from the Mayo Clinic. He added: "Targeting this pathway to decrease the proliferation of cancer cells may represent a new strategy for pancreatic cancer therapy."
Dr Storz said that using a combination of chemotherapy, bortezomib and other inhibitors of molecules activated along the pathway may help pancreatic cancer patients.
"Of course, this hypothesis requires extensive clinical testing, but our findings offer a new direction to investigate in improving treatment of pancreatic cancer," he said.
The study was funded by grants from the American Association for Cancer Research and the National Institutes of Health.