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Understanding changes to metabolism and immune function

Claire Connell

Recipient: Dr Claire Connell

Host Institution: Cancer Research UK Cambridge Institute 

Title: Understanding changes to metabolism and immune function in patients with pancreatic adenocarcinoma

Type of award: 2019 Research Innovation Fund

Funding: £108,000

Cachexia is a specific type of weight loss that cannot be reversed when patients increase their calorific intake; no matter how much you eat, you will continue to lose weight, and effectively starve. Although up to 90% of patients with pancreatic cancer suffer from it, very little is known about what causes this and how to stop or reverse it.

There is a clear need to carry out more work to understand what goes on in the body at the onset of cachexia. Not only does this irreversible weight loss have an extremely negative impact on a patient’s quality of life, but it is thought that it also interrupts the function of a patient’s immune system, preventing potential treatment options such as immunotherapy from working. Immunotherapy has been hugely successful in treating patients with cancers such as leukaemia. A better understanding of cachexia may therefore not only improve quality of life but also unlock the potential of immunotherapy being  effective against pancreatic cancer.

From previous work, Dr Connell’s group identified that pancreatic cancer can stop metabolism (the cellular process that converts food to fuel) from working properly causing patients to become cachexic. This disruption of metabolism also causes an increase in certain hormones, which leads to a reduction in the number of immune cells being produced by the patient’s immune system. The group thinks that this weakening of the immune system is the reason why patients with pancreatic cancer respond so poorly to immunotherapy.

In order to understand this further, the team will compare data on changes in the metabolism and immune system of patients with pancreatic cancer who have cachexia with the results from those who don’t. Analysis of this data will start to give vital insight into why and how so many people with pancreatic cancer suffer from cachexia and how it impacts on response to treatment and what can be done to reverse it.

The results of this study will provide an important foundation for future research to identify treatments to reverse cachexia and improve immune function and response to treatment in people with pancreatic cancer. This has the potential to improve patients’ quality of life, help patients’ to live longer and open up possibilities of developing better treatment options.