- Pancreas cells on the way to cancer form clumps of problem proteins similar to those seen in dementia
- The clumps appear when the cells recycling system breaks down in the presence of a faulty KRAS gene
- Understanding this process may help doctors predict, prevent or slow pancreatic cancer which is often linked with diabetes
Pancreatic cancer is one of the hardest cancers to treat and survival has barely improved compared with some other cancers.
One reason is that it is often found late when treatment options are limited. Researchers funded by Cancer Research United Kingdom have been looking closely at what happens in pancreas cells before cancer takes hold, in the hope of finding earlier warning signs.
A team from the Cancer Research United Kingdom Scotland Centre studied pancreas cells in mice that carried a faulty version of a gene called KRAS.
Changes in this gene are common in pancreatic cancer. The researchers followed these cells over time to see how healthy pancreas tissue gradually shifts towards a pre cancer state.
They found that cells on the verge of becoming cancerous developed problems with their internal recycling system, called autophagy.
Autophagy is the way cells clear out excess or damaged molecules, including proteins they no longer need. In the pancreas it is especially important because the organ produces digestive enzymes and hormones that must be tightly controlled.
When autophagy faltered in these pre cancer cells, unwanted protein molecules began to build up and stick together.
The proteins formed clumps that looked very similar to those seen in some forms of dementia and other neurological conditions.
The same pattern of clumping was also seen in samples of human pancreas tissue, suggesting this is not just a mouse phenomenon.
Why this matters for pancreatic cancer and diabetes
The link between diabetes and pancreatic cancer is complex. Long standing diabetes can increase the risk of pancreatic cancer, and in some cases new onset diabetes can be an early sign that something is wrong with the pancreas. Understanding what happens inside pancreas cells as cancer begins to develop is therefore highly relevant to people with diabetes.
The new research suggests that it is not only gene faults like mutated KRAS that matter.
The way cells handle waste through autophagy also plays a key role. In some cancers, cells become dependent on autophagy to fuel their rapid growth.
Here, the picture is slightly different. The combination of a faulty KRAS gene and a disrupted recycling system seems to create a build up of toxic protein clumps that may push cells further along the path towards cancer.
If scientists can map exactly how these early changes unfold, they may be able to spot future pancreatic cancer sooner, perhaps through blood tests or imaging that detect signs of protein clumping or recycling failure.
In the longer term, treatments that restore healthy autophagy or stop the harmful effects of protein clumps could become part of strategies to slow or prevent the disease.
Where the research goes next
The study was published in the journal Developmental Cell and involved collaborations across several laboratories, including work at the University of Edinburgh.
It is still early stage research, but it opens interesting lines of enquiry.
Next steps include:
- Studying the combined effects of KRAS mutations and autophagy problems in more detail, to understand exactly how they drive cell changes
- Looking at whether age, sex and diet influence how quickly protein clumps build up in pancreas cells
- Exploring whether any of the processes involved can be reversed, slowed or blocked in animal models
Cancer Research United Kingdom has made pancreatic cancer a priority area.
Ongoing projects cover the causes of the disease, better diagnostic tests and new treatment approaches.
For people living with diabetes, especially those with changes in weight, digestion or new symptoms, the message is not to panic but not to ignore new or persistent problems either.
If you notice changes that worry you, speak to your GP so that anything serious can be ruled out or picked up early.
