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Making pancreatic cancer less deadly

Pancreatic cancer survival rates have been improving over the last few decades, but the statistics still make grim reading. According to the America Cancer Society, the one-year relative survival rate for all cases of pancreatic cancer is 20 per cent. Only seven per cent of people diagnosed with the disease survive for five years.

One of the reasons that pancreatic cancer is so deadly is because of a protein known as S100p which is highly expressed in other aggressive cancers too. Once this protein is activated, it signals changes that tell the cancerous cell to grow and divide very quickly, which encourages rapid growth of tumours and metastases around the body.

Scientists at the University of Hertfordshire, in collaboration with Dr Tatjana Crnogorac-Jurcevic of Barts Cancer Institute, Queen Mary University of London, have used computer modelling to design new compounds that could be used therapeutically to prevent S100P from being activated.

In a project funded by the charity Worldwide Cancer Research, Dr Stewart Kirton of the University of Hertfordshire designed the structures of new drugs based on Cromolyn, a drug that can be used to prevent allergy-induced asthma. These new compounds were then synthesised by Hertfordshire’s Dr Sharon Rossiter and her team of chemists.

Researchers screened a bank of 93 synthetic compounds for their ability to prevent the activation of S100P. From that work, 18 potential drugs were identified and then tested to see how toxic they are to cells.

The compounds themselves did not kill the pancreatic cancer cells, but they did prevent them from migrating. This is an excellent profile for a drug to treat this type of cancer, since in theory any drug that worked in this way would both slow down the progression of the cancer and make it more vulnerable to chemotherapy.

The next stages are to look at ways to make sure that there are as few side effects possible by making small changes to the structure of the most promising candidate drugs. If successful, it might make a difference for patients between no survival – and a prolonged life. One day, pancreatic cancer may even become a manageable disease.


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