Science is often surprising. Different fields can cross over in unexpected ways and an accidental discovery might lead to a serendipitous breakthrough, just as an unattended petri dish gave us the world’s first antibiotic.

It’s hard to plan for those kind of advances, but our researchers often explore whether a discovery about how one type of cancer behaves can be applied to other cancer types. And sometimes, they also find links between cancer and different diseases altogether.

That’s what’s just happened at the CRUK Scotland Centre, where Professor Simon Wilkinson’s team have uncovered curious dementia-like behaviour in cells during the development of pancreatic cancer. Their unexpected findings provide clues that could help us stop this especially hard to treat form of the disease, which affects around 10,500 people in the UK every year.

Pancreatic cancer is often detected late, when there are fewer treatment options available. As a result, despite all the advances we’ve made in treating cancer overall, survival for pancreatic cancer hasn’t improved as much as survival for other cancer types.

Wilkinson’s team are trying to change that by studying how pancreatic cancer develops. They’re looking at the genetic factors that we already know are important, and they’re also beginning to unravel other processes happening within our cells. 

Faulty genes aren’t the full story 

Multiple cancer types, including pancreatic cancer, are linked to a faulty mutation in a gene called KRAS. Cells with this mutation are called pre-cancer cells because of their increased risk of developing into cancer.

That’s where Wilkinson’s team started. Using mouse models, they compared healthy pancreatic cells and cells with the faulty KRAS gene to find clues about what has to happen before pancreatic cancer starts.

They studied the mice for several weeks, using different tests and lab techniques to build up a detailed picture of how the pancreas cells changed over time. They also studied human pancreas samples to make sure that what they observed in mice was relevant to pancreatic cancer in humans too. 

Throughout their study, they uncovered something interesting – a cellular process unrelated to the KRAS fault was playing a part in the development of pancreatic cancer. 

Autophagy, the cell’s recycling system 

One of the ways our cells keep us healthy is by breaking down excess molecules they no longer need. They do it through a recycling process called “autophagy”, which cells use to recycled materials and energy stored up in those molecules for other purposes. In the pancreas, it’s especially important for controlling the level of digestive juices that help us break down our food.  

Scientists have studied autophagy in detail over many years, showing that it plays a key role in diseases such as cancer. In some cases, cancer cells can become “addicted” to autophagy, hijacking the recycling process to help cancer cells divide and grow more quickly.

Wilkinson and the team thought that’s what was going to happen in pancreas cells with faulty KRAS genes. They were wrong.

An unexpected discovery  

The team observed that autophagy wasn’t behaving as normal in the pancreatic pre-cancers, but it wasn’t going into overdrive either.  

Instead, the recycling process was breaking down. The cells weren’t clearing excess molecules as efficiently as they normally would. That meant ’clumps’ of unrecycled protein were building up, something usually seen in neurological diseases such as dementia.

The team’s study, published today in Developmental Cell, suggests that the combined effect of the faulty KRAS gene and disruption to autophagy could be driving the development of pancreatic cancer.

“Our research shows the potential role autophagy disruption plays in the beginnings of pancreatic cancer,” says Wilkinson. “While this work is at an early stage, we can potentially learn from research into other diseases where we see protein clumping, such as dementia, to better understand this aggressive type of cancer and how to prevent it.”

Wilkinson and his team now plan to study autophagy in pancreas cells in more detail. They want to identify ways to predict and possibly reverse the start of pancreatic cancer. They’ll also explore whether factors like age, sex or diet play a role. This could potentially help us identify who might be at higher risk of developing pancreatic cancer, making it easier to intervene at an earlier stage.