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KRAS gene mutation needs help to trigger pancreatic cancer

12 September 2012

A study by an international research team has shown that a cancer-causing gene is not enough to trigger the development of pancreatic cancer – a second factor is needed to create a “perfect storm” that allows tumours to form.

The study, led by the US Mayo Clinic, is published in the latest issue of the journal Cancer Cell. It overturns the current belief that a mutation in the gene known as KRAS is enough on its own to initiate pancreatic cancer.   

The findings give crucial clues on how pancreatic cancer develops and why few patients benefit from current therapies. The findings also offer ideas about how to improve treatment and prevention of pancreatic cancer.

The research team discovered that for pancreatic cancer to form, mutated KRAS must recruit a second player – the epidermis growth factor receptor, or EGFR.  The addition of a third genetic factor, known as Trp53, makes pancreatic tumours very difficult to treat.

The scientists also found that EGFR was required in pancreatic cancer initiated by the condition pancreatitis. In experiments where the team blocked EGFR activity in mice, they found that the mice were protected against developing both chronic pancreatitis and pancreatic cancer.

"We believe the perfect storm needed to trigger pancreatic cancer includes KRAS mutations and inflammation in the organ, which then work synergistically to turn on EGFR," says Dr Howard Crawford of the Mayo Clinic, who led the study.

"The bottom line is, without EGFR, tumours don't form - and that was never known before this study," he says. "We also think that inflammation in the pancreas has a big impact on turning on EGFR."

The team believes that the study suggests some patients, such as those with chronic pancreatitis, may be good candidates for treatment with EGFR inhibitors to fight or prevent pancreatic cancer.

Dr Crawford says: "These findings give us some greatly needed clues about how pancreatic cancer develops and progresses. The more we understand about these early tumours, the more we will be able to work on diagnosis and therapy."

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