Gene discovered that drives pancreatic cancer growth

The downregulation of a normally protective gene drives pancreatic cancer growth and aggressiveness.

Researchers from the UK and USA analysed tissue samples from pancreatic cancer patients and healthy people to gain a better understanding of how the regulation of different pathways impacts the development and progression of pancreatic cancer.

Dr Maria Hatziapostolou, lead researcher from Nottingham Trent University's John van Geest Cancer Research Centre, said: 'Pancreatic cancer has the lowest survival of all the 20 common cancers. The survival of patients beyond five years has improved very little for some time and so it's extremely important that we find new ways to better understand this disease, how it spreads and why it is so aggressive.'

While our genetic code is generally the same in each of our cells, genes can be switched on or off via epigenetic modifications, such as DNA methylation. The new research, published in Gastro Hep Advances, showed that DNA methylation leads to the downregulation of a gene called HNF4A, which in turn allows pancreatic cancer to grow more quickly and aggressively.

The researchers used cell lines and mouse models of pancreatic cancer, alongside healthy cells, to get a better understanding of the underlying epigenetic changes and their effects on the development of pancreatic cancer.

They found that HFN4A is suppressed via DNA methylation in pancreatic cancer, resulting in lower protein expression from very early on in the disease. Lower levels of HFN4A in pancreatic cancer tissue samples were also correlated with poor overall patient survival.

'Not only have we uncovered the tumour-suppressive role of HNF4A, but also how it is switched off from the very early stage of the disease. Loss of HNF4A drives pancreatic cancer development and aggressiveness and we now know correlates with poor patient survival,' said Dr Hatziapostolou.

More than half a million people are diagnosed with pancreatic cancer worldwide every year, but only about ten percent will survive for more than five years after their diagnosis. One of the main problems is that pancreatic cancer is often diagnosed at an advanced stage, when fewer treatment options are available.

'Improving our fundamental understanding of what makes pancreatic cancer grow and spread so rapidly is vital if we are to make much needed breakthroughs,' said Dr Chris Macdonald, head of research at Pancreatic Cancer UK. 'This project gives us new information on how pancreatic cancer is able to suppress certain molecules to help it spread aggressively around the body which, in turn, could lead to the development of more effective treatment options in the future.'