Research Innovation Fund
Truly unique and innovative research into the causes, treatment and detection of pancreatic cancer and the support for those with it
People with pancreatic cancer desperately need earlier diagnosis, new treatments and better support, yet there hasn’t been a major breakthrough in decades.
One of the ways in which we hope to drive progress is through our Research Innovation Fund. These awards support pilot work that are high risk but high reward – and will put the researchers in a better position to apply for larger grants to take their work to the next exciting stage.
The Research Innovation Fund scheme is rigorously reviewed on the basis of genuine innovation underpinned by sound research methods delivered by world class expertise. It can focus on any area of research relevant to people with pancreatic cancer.
Case study: Early detection of pancreatic cancer by analysing DNA taken from patient blood
Dr Siim Pauklin from the Botnar Research Centre at Oxford University with his team are testing a new technique to identify the ‘DNA fingerprint’ of pancreatic cancer in the blood of patients. This is the first attempt of its kind to detect the presence of the disease before a tumour has even formed. The success of this project would be an important step in helping to indicate the presence of the disease earlier than ever before.
In 2019, we awarded the team £109,986.
Bringing earlier diagnosis to people with pancreatic cancer is one of the most important challenges in pancreatic cancer research and has been for decades. Despite this, we still do not have a clear indicator in the body that can be used to tell us if cancer is present or at what stage it is – a biomarker. This needs to change.
Case study: Combining viruses and ultrasound to better target and destroy pancreatic tumours
Professor Gail ter Haar and her team at The Institute of Cancer Research will take their expertise from delivering ultrasound in other physically similar cancer types and apply it in pancreatic cancer. They have developed an ultrasound technique that will be tested to see how it affects the permeability of the pancreatic cancer tumours. Alongside this, they will also be testing specially engineered viruses designed to target pancreatic cancer cells and cause them to burst, allowing the immune system to destroy them. These strategies will be tested in combination with one another to examine the effect on tumour growth. The potential of this combination is exciting and could help to ensure that people diagnosed with pancreatic cancer have better treatment options.
In 2019, we co-funded £109,575 with the Focused Ultrasound Foundation
We believe that ultrasound exposure of the pancreas will open up the tumour structure and allow better access for new treatment strategies, and also existing therapies, to the tumour cells. If this works as predicted, ultrasound will provide a new, minimally invasive technique for the enhancement of treatment of pancreatic cancer.
Find out more about all of our Research Innovation Fund 2019 projects:
Early detection of pancreatic cancer by analysing DNA taken from patient blood
Recipient: Dr Siim Pauklin
Host Institution: Botnar Research Centre at the University of Oxford
About the study: Bringing earlier diagnosis to people with pancreatic cancer is one of the most important challenges in pancreatic cancer research and has been for decades. Despite this, we still do not have a clear indicator in the body that can be used to tell us if cancer is present or at what stage it is – a biomarker. This needs to change.
The team at Oxford have proposed a novel approach to identify a biomarker from patients DNA for early stage pancreatic cancer. DNA can be modified by attaching and removing chemicals to turn genes ‘on’ and ‘off’. This is normally a crucial and highly regulated process in development and maintenance of health. In cancer, the way these modifications are made becomes unregulated and drives the basic processes that create cancer. However, they also represent a very effective indicator of early cancer development and as such present an opportunity to develop early diagnostic biomarkers for pancreatic cancer.
Dr Pauklin will assess how DNA modifications produce so called ‘cancer stem cells’ – one of the first steps in cancer development. Cancer stem cells are very dynamic and can, on their own, form the whole tumour as well as dictate how aggressive the cancer can become, and how resistant it will be to treatment.
The funded research will work to understand: 1) the basic processes in the cancer stem cells that add and remove DNA modifications 2) the profile of these modifications on DNA from cancer stem cells and 3) if this unique modification profile can be detected in the blood.
A multidisciplinary team of researchers and clinicians working together will deliver this work. They will combine expertise in molecular mechanisms of pancreatic cancer formation with clinical collaborators who will obtain samples from pancreatic cancer patients via the Oxford University Hospitals NHS Foundation Trust.
60% of people with pancreatic cancer are diagnosed at stage 3 and 4, where their hope of treatment, let alone survival, is all but none. A biomarker that is based on the early processes that drive pancreatic cancer development will help deliver early diagnosis to everyone and potentially save more lives. Moreover, understanding more about basic processes in cancer cells could also form a basis for new therapies that stop the development of cancer stem cells altogether.
Combining viruses and ultrasound to better target and destroy pancreatic tumours
Recipient: Professor Gail ter Haar
Host Institution: The Institute of Cancer Research
Funding: £109,575 co-funded by Pancreatic Cancer UK and the Focused Ultrasound Foundation
About the study: Treating pancreatic cancer can be tough for a number of reasons: It’s tough to diagnose; tough to treat; and tough to research. But pancreatic cancer is literally tough. As it grows, the cancer forms a dense, fibrous cage that encases the cancer, preventing treatments and even the body’s own defences from accessing the cancer cells. This research aims to overcome this crucial physical barrier to treatment which could make existing treatments much more effective in the context of pancreatic cancer.
The team at the ICR will take their expertise from delivering ultrasound in other physically similar cancer types and apply it in pancreatic cancer. They have developed an ultrasound technique that will be tested to see how it affects the permeability of the pancreatic cancer tumours.
In parallel, specially engineered viruses that specifically target pancreatic cancer cells will be developed and refined. Their aim is to cause a chain reaction whereby cancer cells burst releasing molecules that the body’s own immune system then recognises. This will allow a mass infiltration of immune cells that can destroy similar cancer cells.
The work will culminate by combining the most effective ultrasound approaches and most efficient virus’s and then testing the combination to see if this inhibits tumour growth and improve survival. The ultimate aim: to break down the barriers and let these virus’s initiate an immune chain reaction that destroys the cancerous cells.
Numerous interventions have been tried, tested and failed in pancreatic cancer and a lot of that is down to tumour permeability. Not only does this study aim to test a new exciting combination, but the ultrasound treatment alone could greatly enhance the effectiveness of other therapies new and old alike, ensuring that people diagnosed with pancreatic cancer have better treatment options.
PancREatic Cancer: Individualised Supervised Exercise study
Recipient: Dr Gillian Prue
Host Institution: Queen’s University Belfast
About the study: Surgery is the only known cure for pancreatic cancer. However, it is an extensive and traumatic procedure. The surgery itself can take up to 12 hours, in an area of the body that is highly perfused with blood vessels and ultimately removes whole sections of the gastro-intestinal system. Even after a patient going through all that, surgery is then followed by chemotherapy. This makes for a huge side effect burden (pain, fatigue, weight loss, bowel issues, nausea) and significantly impacts on recovery and prognosis. To be able to mitigate any of these effects would make these interventions more tolerable, improving the patients’ quality of life as well as their overall prognosis.
The team in Belfast, will build on previous effective studies in breast, prostate and colorectal cancer, to test a bespoke exercise programme for people with pancreatic cancer who have undergone surgery and receiving chemotherapy. It sounds counterintuitive but exercising during cancer treatment can help manage many of the common symptoms such as pain, fatigue and anxiety. The team will work extensively with people affected by pancreatic cancer to design bespoke exercise programs that are tailored and sensitive to their specific side effects. This is a feasibility study that will test this approach in a small number of people. They will evaluate the data from this initial testing and then further develop and enhance the approach to be taken on a larger trial.
Thousands of people are affected by pancreatic cancer right now. It is therefore vital that as well as seeking much needed breakthroughs in developing new treatments that we also fund innovative work that can help patients by making the treatments that are currently available as effective and sensitive as possible in the short term. This exciting study has the promise of giving people undergoing treatment for pancreatic cancer a better quality of life, improved recovery and longer life.
Understanding changes to metabolism and immune function
Recipient: Dr Claire Connell
Host Institution: Cancer Research UK Cambridge Institute
About the study: 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.
Cutting off the energy supply to pancreatic cancer cells
Recipient: Dr Robin Ketteler
Host Institution: University College London
About the study: 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.
Strengthening the immune system’s ability to fight pancreatic cancer
Recipient: Mr Siong-Seng Liau
Host Institution: MRC Cancer Unit at the University of Cambridge
About the study: The potential of immunotherapy (the Nobel prize winning technique of enhancing the body’s own immune system to fight cancer cells) in pancreatic cancer is huge. This therapy has been heralded by the cancer research community as a miracle intervention, with recent studies demonstrating its ability to eradicate leukaemia and breast cancer. However, to date transferring this game-changing intervention into pancreatic cancer has not been successful. There are a number of reasons for this but a crucial barrier is the way pancreatic cancer cells that should be susceptible to immunotherapy, hide themselves from the immune system. Immunotherapy could be a reality for people with pancreatic cancer if we could prevent this immune evasion.
Mr Liau and the team will use specialist laboratory techniques to look at how these cells switch off the expression of certain genes, so called ‘gene silencing’, that allow the cancer to evade the immune system and as such render immunotherapy ineffective. A better understanding of this process will then be used to target the cause of the gene silencing that could potentially remove the barrier to immunotherapy.
There are outrageously few therapies for pancreatic cancer. Only one drug (PEGPH20) has ever been developed specifically for pancreatic cancer and it is currently at a very early stage of development. Surgery is only available to a select few. This project could potentially open the door to a new world of proven, highly effective treatments.