Tackling a mysterious process
There is a feeling that neglected cancers need more research and Pancreatic cancer is one of the least studied. Today, the survival rate is 3% for five years. Professor Petersen, at the School of Biosciences at Cardiff University, hopes his team’s research can change that.  His interest in the pancreas began as medical student in Copenhagen, where he found himself teaching physiology and realised that there was limited understanding of the mechanisms controlling the crucial digestive enzyme secretions. His study of the molecular processes of the normal pancreas moved on to pathological problems.

Controlling cell signalling
In conditions of pancreatitis (which can lead to pancreatic cancer) the enzymes, produced by the pancreas and needed for food digestion, become excessive and digest the pancreas itself. Alcohol abuse, or gallstone complications, can cause excessive calcium signals, triggering the secretion of digestive enzymes inside the organ. Petersen’s team are finding a way to reduce these calcium signals. Petersen explains, ‘a calcium-binding protein called calmodulin is present in all cells, so when the calcium concentrate goes up, this protein gets activated. It’s a normal protective function, but when the calmodulin protein is missing the calcium signals increase.’

Their thinking is that if they can activate the calmodulin protein, it would provide a protective mechanism. In the lab they have found a tiny calcium-like peptide that can pass through cell membranes, activating calmodulin to reduce the secretion signals. This is potentially a way of curing an acute attack of pancreatitis. A major part of their research funding is to take this work further and understand fully how the calcium peptide works.

Anti-cancer properties
Stellate cells are another key part of the project. According to Petersen, ‘these mysterious cells are present in the normal pancreas in very small numbers, but in chronic pancreatitis they proliferate and produce a matrix which is cancer promoting. We need to understand how this cell division of stellate cells is controlled. Again calcium signalling appear to be involved.’

He thinks it possible that the stellate cells are always important to the development of pancreatic cancer, and not just where chronic pancreatitis is present. Their project has a long timeline but the team at Cardiff University are determined to find a therapy that takes advantage of their better understanding of cell signalling.