2025 Early Detection Grant - Dr. Chamini Perera

Pancreatic cancer is often hard to detect early because its symptoms are vague and  there are no simple tests that can reliably catch it before it spreads. Testing everyone in  the population is not practical and economical, but scientists are looking at people who  may be at higher risk. For example, those who recently diagnosed with a certain type of  diabetes that is linked to pancreatic cancer, called pancreatic cancer-related diabetes  (PCRD). 

This special type of diabetes tends to occur 3 to 5 years before the cancer diagnosis,  which gives doctors a crucial window to spot early warning signs before the pancreatic  cancer becomes serious. In previous studies, we found that tiny particles (termed  exosomes) released by early cancer cells with specific gene mutations (called Kras and  p53) may interfere with the pancreas’s ability to regulate blood sugar. These particles  seem to damage insulin-producing cells, possibly contributing to PCRD. We also  observed for the first time that i) high sugar containing diet can support cancer  progression in an animal model of pancreatic cancer and ii) several proteins and RNAs  are packaged within small particles (exosomes) that are secreted by PC cells and their surrounding cells (pancreatic stellate cells) are known to play a role in glucose  metabolism and/or pancreatic cancer. 

On top of that, the blood vessels around these insulin producing cells, normally  supported by specialised cells called endothelial cells and pericytes can also  malfunction, adding to the trouble. When these blood vessels do not work properly, the  pancreas struggles to manage blood sugar, leading to high glucose levels. In our study,  we are investigating how these mutated early cancer cells and other cells in the  pancreas (called stellate cells) affect the small blood vessels around insulin-producing  cells. We believe this disruption may be a key factor in causing high blood sugar levels  and may even help fuel the growth of cancer. 

By studying these interactions closely in both mouse and human cells and also mouse  models, we aim to identify factors that act as early warning signals. These factors then  can be developed as biomarkers that doctors could one day use to detect pancreatic  cancer much sooner. Also, understanding these changes could also help uncover new  treatment strategies. If pancreatic cancer is detected early, while it is still possible to  remove it surgically and before it spreads, patients may have more options. That means  a better chance at recovery, fewer emotional and physical stresses on families, and a  higher quality of life for everyone involved.