Researchers at Barts Cancer Institute at Queen Mary University of London, supported by a partnership between the UK charities Worldwide Cancer Research and Pancreatic Cancer Research Fund, have made a discovery that reveals new insight into how healthy cells help pancreatic tumours develop, which they hope will lead to the development of new drugs for this hard to treat cancer.
To improve the outcomes for patients, we need to identify new strategies to target cancer cells as well as the normal cells supporting cancer growth, and find ways to help the body’s immune system fight back against cancer.
Pancreatic cancer remains one of the hardest to treat types of cancer – fewer than 1 in 10 people in the UK are expected to survive 5 years or more after diagnosis.
Pancreatic tumours are often surrounded by a dense stroma, or ‘scar tissue’, produced by cells called fibroblasts. The stroma blocks chemotherapy from reaching the tumour and suppresses the immune system, making immunotherapy ineffective.
This new research, led by Dr Angus Cameron, found that blocking expression of a protein, called PKN2, changed the behaviour of healthy cells around the tumour. These cells, called fibroblasts, which are highly mobile and invasive, not only protect pancreatic cancer from treatment, but also aid in spreading it around the body. The researchers therefore hope that targeting fibroblasts to change their behaviour could affect how pancreatic cancer develops.
When the researchers blocked expression of PKN2 in the healthy cells of a pre-clinical model of pancreatic cancer, the tumour grew more aggressively. However, the fibroblasts switched to a less mobile and invasive state and instead promoted inflammation – this is known to make tumours more aggressive but can also make them more responsive to immunotherapy.
The findings of this study expose PKN2 as a potential new drug target to alter the development and treatment sensitivity of pancreatic cancer.
Dr Cameron and his team are now studying the altered profile of immune cells within pancreatic cancer tumours. In future, the right combination of immunotherapy and a PKN2-targeting drug could be an effective way of treating pancreatic cancer.
Dr Cameron added:
"Our study contributes to the understanding of the biology of the invasive process in pancreatic cancer, and the roles that fibroblasts play. In our future work, we hope to identify effective drugs to target PKN2, which can be used in laboratory models of pancreatic and other cancers.
This will allow us to test how targeting this pathway changes the way cancers develop, which is a key step towards clinical application.”
Pancreatic cancer remains stubbornly stuck as one of the least survivable cancers, with fewer than 1 in 10 people living 5 years after diagnosis. It is difficult to treat because current cancer drugs do not work well, so for people with pancreatic cancer to have a better outlook we must find completely new ways to treat it. By supporting innovative cancer research projects like that of Dr Cameron and enabling the brightest minds around the world to investigate new ideas, we can have hope for new cancer cures in future.
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