Scientists have found that precancerous pancreas cells may behave like dementia-affected brain cells, forming toxic protein clumps when their recycling system falters.
Scientists have identified dementia-like activity in pancreatic cells that are at risk of becoming cancerous. These findings may provide important insights for developing strategies to treat and prevent pancreatic cancer, a particularly hard-to-treat disease responsible for around 6,900 deaths each year in the UK.
The study, published in Developmental Cell, was funded primarily by Cancer Research UK, with additional backing from Wellcome, the Medical Research Council, and the Biotechnology and Biological Sciences Research Council.
At the Cancer Research UK Scotland Centre, researchers tracked pancreatic cells in mice over time to investigate why normal cells begin transforming into cancer cells. They found that pre-cancerous cells develop defects in the process of autophagy, the recycling system cells use to break down and reuse unneeded components.
Protein clumps link cancer and dementia
In pre-cancerous cells, the researchers observed an accumulation of “problem protein” molecules that clustered together — a phenomenon also seen in neurological conditions like dementia. Similar clumping was detected in human pancreatic tissue samples, indicating that this process may occur during the early stages of pancreatic cancer.
Cancer Research UK Senior Fellow at the Institute of Genetics and Cancer at the University of Edinburgh, Professor Simon Wilkinson, said: “Our research shows the potential role autophagy disruption plays in the beginnings of pancreatic cancer. While 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.”
Why pancreatic cancer is difficult to treat
While survival rates have risen for many forms of cancer in recent decades, pancreatic cancer remains an exception. One reason is that it is frequently detected only at advanced stages, when treatment choices are far more limited. To better understand this disease, the researchers set out to investigate what drives normal pancreatic cells to become cancerous.
Although mutations in the KRAS gene are strongly associated with several cancers, including pancreatic cancer, scientists are increasingly recognizing that genetic alterations alone cannot fully explain how the disease develops.
One of the ways cells keep people healthy is by breaking down excess molecules they no longer need, through a recycling process called “autophagy.” Autophagy is particularly important in the pancreas to control the level of digestive proteins and hormones the pancreas produces to help break down food.
The role of autophagy in cancer
Scientists have studied autophagy in detail over many years and are learning the key role it plays 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.
This research, on the other hand, suggests the combined effect of the faulty KRAS gene and disrupted autophagy could be driving the development of pancreatic cancer. The researchers plan to study these processes in more detail, to see if they can help predict or possibly reverse the start of pancreatic cancer, and if factors like age, sex, or diet play a role.
Executive Director of Research and Innovation at Cancer Research UK, Dr. Iain Foulkes, said: “Around 10,500 people are diagnosed with pancreatic cancer in the UK each year and, sadly, too many of those cases are found at a stage where treatment options are limited. While further work is needed, these findings could provide vital clues into how we can better understand how pancreatic cancer develops.”
Reference: “ER-phagy and proteostasis defects prime pancreatic epithelial state changes in KRAS-mediated oncogenesis” by Carla Salomó Coll, Marisa Di Monaco, Jocelyn Holkham, Matthew Smith, Morwenna Muir, Philippe Gautier, Hywel Dunn-Davies, Xiaozhong Zheng, Roopesh Krishnankutty, Alain J. Kemp, Katie Winnington-Ingram, Alex von Kriegsheim, Jennifer P. Morton, Natalia Jimenez-Moreno, Damian Mole and Simon Wilkinson, 14 August 2025, Developmental Cell.
DOI: 10.1016/j.devcel.2025.07.016
Funding: Cancer Research UK, Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council
Never miss a breakthrough: Join the SciTechDaily newsletter.