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Cutting off the energy supply to pancreatic cancer cells

Recipient: Dr Robin Ketteler 

Host Institution: University College London 

Title: Cutting off the energy supply to pancreatic cancer cells

Type of award: 2019 Research Innovation Fund

Status: Live

Funding: £109,340.68

Autophagy is used to describe the process where cells consume parts of themselves to improve their energy supply and survival. Tumour cells grow more rapidly than normal cells, meaning that they require a lot more energy than is readily available. They are therefore dependent on autophagy to fuel this need for rapid growth.

Previous research has shown that autophagy plays a key role in not only helping pancreatic cancer cells to expand and survive but also to increase resistance to current treatment options such as chemotherapy and radiotherapy. If this process can be slowed down or stopped completely, the cancer cells will die and the tumour will shrink. However, the mechanism by which autophagy helps pancreatic cancer cells to survive is still relatively unclear and drugs that specifically target autophagy and stop the process have not yet been identified.

This project aims to build on pioneering work in this field by bringing together experts in autophagy and drug discovery to work towards developing a targeted therapy that disrupts the autophagy process in pancreatic cancer. This is an up and coming area of research across the cancer field and presents an exciting opportunity to develop ground-breaking new treatment options for pancreatic cancer.

In previous work, the team found that a gene called ATG4B plays an important role in autophagy. In this study, they will be using computer modelling to screen ~1.5 million compounds to identify which ones are successful at targeting and inhibiting the effects of ATG4B in pancreatic cancer cells.

A group of these compounds will then be tested on lab grown 3D mini tumours. These mini tumours model a similar environment and structure to that of a tumour in a patient, allowing the team to establish whether the compound successfully targets ATG4B and stops autophagy, causing the cells to die and halting or even reversing tumour growth.

This Research Innovation Fund project has the potential to open the door for the development of new treatment options to target pancreatic cancer. The project has the potential to unlock an effective method for significantly slowing down tumour growth in patients as well as improving the effectiveness of other existing treatment options. This will provide a vital lifeline to pancreatic cancer patients that otherwise have very few options available to them.