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Pancreatic cancer researchers harness CRISPR gene editing to slow down disease spread

Posted by: Research 10 May 2018

A team of researchers funded by Pancreatic Cancer UK have found a way to slow down the growth and spread of this tough cancer, and they could soon improve the chances of chemotherapy treatment being effective, findings published today (Thursday, 10th May) in Nature Communications.

The team at Imperial College London, led by Dr Leandro Castellano, looked at a set of molecules called microRNAs, which are found in abundance in pancreatic cancer stem cells. These molecules work with a chemical hormone called tgf beta, which controls cancer cell behaviour, and together they encourage pancreatic cancer cells to grow and spread. Dr Castellano set out to investigate whether removing the microRNAs in pancreatic cancer would mean that this process could be slowed down, to improve the prognosis of a disease which 80 per cent of patients are diagnosed with at an advanced stage and which less than seven per cent of patients survive beyond five years.

Using the cutting-edge CRISPR gene editing technique, Dr Castellano and his team created pancreatic cancer cell lines in the lab without microRNAs and were then able to stop the process between microRNAs and tgf beta from happening, and therefore slowed down the growth and spread of the disease. The team then took their findings a step further within the same study. They investigated the same process in mice with pancreatic cancer, and once again found that removing the microRNAs meant that the growth and spread of the disease was slowed down.

Dr Castellano and team now plan to investigate whether removing the microRNAs will prevent a key process which normally takes place to develop the stroma. The stroma is the ‘armour’ which surrounds a pancreatic cancer tumour, and makes it very difficult for treatments such as chemotherapy to reach the tumour, which is why finding new ways of weakening the stroma is a key challenge for pancreatic cancer researchers. If in the future this ‘armour’ could be weakened in people with the disease, it could mean that chemotherapy could reach tumours more effectively, in turn allowing patients to live for longer.

The hope is that Dr Castellano’s research could in the future lead to a new treatment which could not only slow down the growth and spread of this tough disease, but also weaken the ‘armour’ of the stroma and improve the effectiveness of chemotherapy.

Dr Castellano said: “Sadly by the time people are diagnosed with pancreatic cancer, all too often the disease has spread to other organs. And treatment for pancreatic cancer is often not very effective, because the stroma makes it so difficult for treatment to reach the tumour and fight the disease. It is therefore vital that new ways are discovered to slow down the growth and spread of this disease, and also to improve the effectiveness of treatment. Our research was a great success in that we made progress towards tackling both these problems.

“We are very much looking forward to taking this important work to the next stage. We now need to carry out more research in mice looking at tgf beta and whether we can weaken the stroma and allow chemotherapy to be more effective, and we hope that if that is successful then we could move our research to a clinical trial in the next few years.”

Leanne Reynolds, Head of Research at Pancreatic Cancer UK, said: “We are incredibly proud to have funded this cutting edge research, which has not only found a crucial new way of slowing down the growth and spread of this tough cancer, but is also paving the way for more effective chemotherapy treatment for patients in the future.

“The potential positive impact which these results could have on patients’ lives in years to come is significant. If future research is successful, Dr Castellano’s results could lead to many pancreatic cancer patients living longer and having more precious time with their families. This research is a shining example of the kind of work we want to fund through our Research Innovation Fund. It is truly dynamic research which harnesses the very latest techniques which science can offer us, and forges ahead to bring about lasting change for patients, by investigating a major challenge in pancreatic cancer.”

Pancreatic Cancer UK funded the research through a £69,000 grant from its Research Innovation Fund scheme. In July, the charity will be calling on researchers to apply for its next round of grants from the scheme.

For more details visit our Research page.