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Slowing the growth and spread of pancreatic cancer using CRISPR

Recipient: Dr Leandro Castellano

Host Institution: Imperial College London

Title: Harnessing the CRISPR gene editing technique to slow pancreatic cancer

Type of award: 2016 Research Innovation Fund

Funding: £69,950

Slowing down the growth and spread of pancreatic cancer

Pancreatic cancer is incredibly complex, involving multiple different cell types. Many tumours are resistant to treatment by chemo - and radiotherapy.

We need to know more about pancreatic cancer progression and resistance to therapy to understand why the disease does not respond well to the cancer drugs that are available.

Leandro Castellano

With Pancreatic Cancer UK funding, Dr Leandro Castellano’s team took a deeper look at cancer stem cells, a subpopulation of cells that grow, can produce new cancer cells and are resistant to existing treatments. Dr Castellano identified a set of molecules that are found in abundance in these cancer stem cells called microRNAs.

He predicted that reducing the levels of these microRNAs would make pancreatic cancer cells become less mobile and the population of cancer stem cells reduce drastically.

These microRNA 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.

Cutting-edge CRISPR technology

Dr Castellano set out to investigate whether removing the microRNAs in pancreatic cancer would mean that this process could be slowed down.

Using the cutting-edge CRISPR gene editing technique, Dr Castellano and his team created pancreatic cancer cell lines in the lab without microRNAs.

Excitingly, they were then able to stop the process between microRNAs and TGF beta from happening, and slowed down the growth and spread of the disease.

The team then took their findings a step further within the same study, investigating 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. This work is now published in the high-impact journal Nature Communications.

Moving closer to a new treatment

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 ‘armour’ which surrounds a pancreatic cancer tumour, and makes it very difficult for treatments such as chemotherapy to work well.

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."