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Understanding the impact of the immune system on response to treatment in pancreatic cancer

Recipient: Asmita Thapa (Future Leader)

Recipient: Professor Eric O’Neill

Host Institution: University of Oxford

Title: Understanding the impact of the immune system on response to treatment in pancreatic cancer

Type of award: 2015 Future Leaders Fund

Funding: £100,000

Why are we funding this research?: Current treatment options for pancreatic cancer are limited, and most patients diagnosed with the condition have a poor outlook, especially if their condition is advanced. Many tumours are resistant to treatment by chemotherapy and radiotherapy and we desperately need to understand more about the reasons for this.

What we the team hoping to achieve?: Pancreatic cancer is unique from other cancers in that the mixture of cells and proteins that surrounds the cancer cells, otherwise known as the tumour stroma, is particularly dense and can make up to 90% of the tumour mass. This stroma can also become infiltrated will a specific type of immune cell which prevents chemotherapy from working properly. The immune cells do this by a dual approach; by preventing the ‘good’ immune system from working properly and by converting the cancer cells into cells that are more resistant to treatment.

This project will investigate the second puzzle - how the immune cells promote cell conversion. Future Leader Asmita will also investigate the process through which normal cells in the pancreas transform into malignant tumours. The ultimate aim will be to discover markers in the body that signal that pancreatic cancer is developing in order to identify potential new cancer drugs that can stop these events, and even play a role in developing methods to detect pancreatic cancer earlier. 

What has been achieved in the first year?: Asmita’s first aim has been to investigate the early stages of pancreatic cancer development, particularly focusing on molecular markers that are important in driving the process. She has identified a particular protein called ‘YAP’, which seems to play a role in the progression of pancreatic ductal adenocarcinoma (or PDAC), the most common type of pancreatic cancer. Upon investigation of this YAP protein, Asmita found that it cooperates with an oncogene called KRAS which controls cells creation. KRAS is found to be mutated in around 95% of patients with pancreatic cancer. This suggests that YAP plays a part in pancreatic cancer cells developing from pre-cancerous lesions in the body.

Using these insights, further research might show that the detection of YAP might represent an option as an early diagnosis biomarker, as it seems to be expressed in the early stages of pancreatic cancer development. Furthermore, cancer drugs that stop YAP from causing pancreatic cancer to progress could be developed, which could halt the disease in its tracks before it reaches an advanced stage.

What will Asmita be doing in the next year?: Building on this great start, Asmita and the team in Oxford will focus mainly on confirming their observations around YAP and its role in pancreatic cancer development.