New research into the chemical messages that travel between cells has found a way to significantly reduce the ability of pancreatic cancer cells to spread.
In laboratory experiments, researchers from Barts Cancer Institute, Queen Mary University of London, have discovered how a protein, Fibroblast Growth Factor Receptor 1 (FGFR1), plays a vital role in enabling the spread of pancreatic cancer. They found that by blocking this protein in the healthy cells that support the tumour they were able to reduce the spread of cancer.
Dr Coetzee with her daughter Matilda and Professor Grose
To understand how tumours spread, the researchers developed a 3D model of pancreatic cancer, made up of cancer cells and healthy cells embedded in an artificial gel resembling the tumour environment.
Typically, a pancreatic cancer tumour surrounds itself with a thick fibrous layer of healthy cells, known as the ‘stroma’, which acts as a barrier and can make treatment, such as chemotherapy, ineffective. The researchers’ 3D model included both cancer cells and ‘stellate’ cells, which make up a large proportion of the stroma. By watching the cancer develop within the model, the researchers saw that it was the stellate cells that typically led the invasion into the surrounding material, with the cancerous cells following behind.
The team were interested in the chemical messages within the Fibroblast Growth Factor (FGF) ‘signalling pathway’, which is important during embryonic development and wound repair, but is under tight control and usually switched off in adults. If reactivated inappropriately in adults, it is thought to play a role in many cancers. When the researchers blocked a key protein in the pathway, FGFR1, they found it halted the pancreatic cancer’s spread.
Surprisingly, the researchers found that FGFR1 was activated in these healthy stellate cells rather than the cancerous cells. This suggests that the healthy stellate cells are a key driver of cancer spread and that targeting them with drugs would be beneficial in pancreatic cancer treatment.
The researchers also carried out some initial tests on mice, using a drug that blocks FGFR1 alongside two other chemotherapy drugs. This would be the most likely route for its use in treating pancreatic cancer, according to Dr Abigail Coetzee, who was involved in the research as part of her PhD, funded by PCRF.
Dr Coetzee said: “While this approach could help in slowing down the spread of cancer cells, since it isn’t toxic to the cancer, it couldn’t be used as a treatment on its own. This was why we tested it alongside a chemotherapy. Our initial results were definitely encouraging, but more work needs to be done before this could move forward to a clinical trial.”