Current treatments for pancreatic cancer are limited, and patients are often too unwell to tolerate the challenging side-effects they cause. It is vital that we learn how to treat pancreatic cancer better to improve both survival and quality of life.
Pancreatic cancer is a very challenging disease to treat, and there is still a lot we don’t know about how it grows and spreads. Tumours are surrounded by a tough outer layer of scar-like tissue, which makes it difficult for drugs to reach and destroy the cancer cells. Pancreatic cancer is also very aggressive, which means that it spreads quickly around the body and is very good at hiding from the immune system.
Despite these challenges, thanks to your support, we are making progress in understanding pancreatic cancer and how we can target its weaknesses. This is an exciting time for research in this area with new treatments – including KRAS inhibitors, immunotherapies and cancer vaccines – on the horizon, all of which could be game changing.
Here, we explore how research we’ve funded is already helping to discover and develop new treatments, as well as making current treatments more effective.
"We have a duty to start developing new treatments now or else when we achieve breakthroughs in earlier detection, we still won’t be able to treat people. We need to find novel ways to better understand tumours to identify effective treatments and change the outcomes for patients"
Improving our understanding of pancreatic cancer
It is crucial that we improve our knowledge of the biology that underpins the growth and development of pancreatic cancer tumours, so that we can identify weaknesses that could be targeted with new treatments.
Pancreatic cancer cells are very resilient and can survive in conditions inside tumours where a healthy cell cannot. For instance, they can continue to grow in areas where a healthy cell’s normal fuel source, glucose, is not available. With our support, Dr Anguraj Sadanandam and his team at the Institute of Cancer Research in London found that pancreatic cancer cells can adapt and use a different emergency fuel source to stay alive. This critical finding could provide a new target for pancreatic cancer treatment.
Our researchers also discovered that pancreatic cancer can “switch off” a gene called HNF4A, which enables it to become more aggressive. Research that we part-funded at Nottingham Trent University led by Dr Maria Hatziapostolou showed that when this gene is switched off, pancreatic cancer can grow rapidly. This project shed new light on how pancreatic cancer suppresses certain molecules to help it spread aggressively around the body. This new knowledge could lead to the development of more effective treatment options in the future.
Unfortunately, many patients with pancreatic cancer relapse and develop resistance to chemotherapy, even after surgery. To better understand how chemotherapy resistance develops over time, Professor Axel Behrens from the Institute of Cancer Research in London developed a new method of carrying out ultrasound-guided biopsies of pancreatic cancer tumours in mice. This allowed researchers to study the development of chemotherapy resistance for the first time. Using this new technique, the researchers identified 16 proteins that may be involved in helping cancer cells survive chemotherapy. They found that these proteins are involved in two biological processes that create inflammation in the body. Further work is now required to find out how inflammation could help cancer cells adapt and survive chemotherapy and could, in future, inform future clinical trials.
Targeting the tumour
Pancreatic cancer tumours are unique in that they are surrounded by a tough layer of scar-like tissue, called the stroma. This acts as a physical barrier, helping cancer cells hide from the immune system, and stops drugs such as chemotherapy from reaching and destroying cancer cells. Disrupting this physical barrier could make treatments more effective.
Thanks to our funding, Professor Gail ter Haar and Dr Petros Mouratidis at the Institute of Cancer Research in London found that a technique called High Intensity Focused Ultrasound could improve the ability of drugs, such as immunotherapy, to get into pancreatic cancer tumours. Following this exciting finding, we awarded Dr Mouratidis a Career Progression Fellowship to investigate this further. This award provided more evidence to suggest that focused ultrasound has great potential to improve the treatment of pancreatic cancer, either alone or in combination with immunotherapy, possibly due to changes in the immune response. The team now hope to secure more funding to take this closer to clinical trials.
Radiotherapy currently has limited benefits as a treatment. This is because the pancreas sits very close to other organs and is constantly moving; this impacts how much radiation can be safely given without harming healthy organs nearby.
FLASH radiation is a relatively new type of radiation which uses an extremely high dose (higher than the standard dose) over a short period of time. This radiation can kill tumour cells, like standard radiotherapy, but causes less damage to surrounding healthy tissue, reducing side effects and improving quality of life. We supported Dr Eui Jung Moon and her team at the University of Oxford to investigate whether FLASH radiation is an effective treatment for pancreatic cancer. They found that FLASH radiation, as well as standard radiation, both increased survival in a mouse model of the disease. In addition, there was a significant increase in white blood cells following FLASH radiation, suggesting that this treatment may boost the ability of the immune system to target cancer cells. In the future, FLASH radiation could be a new treatment option for pancreatic cancer.
Boosting the immune system
Immunotherapy is a type of treatment which harnesses the power of the body’s own immune system to recognise and destroy cancer cells. It has been very successful in treating some kinds of cancer, for example blood cancers, but so far has not had the same effect in pancreatic cancer. Our funding has helped develop novel immunotherapies that we hope could soon be used to treat pancreatic cancer.
Cancer-destroying viruses are a type of immunotherapy that have shown promise as a treatment option for some cancers. These viruses have been engineered in the lab to destroy the cancer cells, whilst simultaneously triggering the body’s immune system to recognise and attack cancer cells.
In 2011, we funded Professor Yaohe Wang at Barts Cancer Institute, London, to create modified viruses which work against pancreatic cancer cells. This work was highly successful and led to the development of a new therapy, which is now entering clinical trials. If shown to be effective, these viruses could provide an effective new treatment option for people with pancreatic cancer.
Scientists have also recently learnt how to modify immune cells, called T cells, so that they specifically attack the cancer without also destroying normal healthy cells, reducing unwanted side-effects of treatment. These customised cancer-fighting cells are called CAR-T cells. CAR-T cell therapy has revolutionised the treatment of some cancers, including leukaemia, which was previously hard to treat. However, so far, it has not been effective for pancreatic cancer.
In 2017, we funded the Pancreatic Cancer UK Grand Challenge award, led by Professor Nick Lemoine, Professor John Marshall, Professor Yaohe Wang and a team of researchers at Barts Cancer Institute (Queen Mary University of London) and King’s College London. They focused on trying to overcome some of the challenges in using immunotherapy for pancreatic cancer and working out the best way to combine immunotherapy with viruses that selectively destroy tumour cells, to develop a new treatment approach.
The findings from the Grand Challenge award have increased our knowledge of the potential of CAR-T cells and tumour-targeting viruses for treating pancreatic cancer and laid vital groundwork for future research, which could ultimately lead to the development of new, more effective treatments.
The researchers are now considering how to translate their findings for use in people and have so far leveraged further funding of over £3.6 million to continue this research.
"After more than 30 years working in pancreatic cancer research, I am more optimistic than ever that we can develop an effective therapy for this dreadful disease."
Making current treatments better
Our researchers are also helping make progress towards improving and speeding up patient care.
We funded a team in University Hospital Birmingham, led by Professor Keith Roberts, to develop a ground-breaking Fast Track Surgery Model. The team worked with hospitals to speed up referrals for patients and reorganised the way surgery was carried out. In this pilot study, 97% of patients who were eligible for surgery went on to have the treatment successfully, compared to a current average of 75% of eligible patients.
Previously, there was no single way for health professionals to report findings of tests for pancreatic cancer, such as scans, making it difficult for them to make fast and effective decisions on how to treat a patient. We supported a national team of pancreatic cancer specialists to develop a tool, called PACT-UK, that could help standardise how pancreatic tumours are characterised in terms of their shape and structure. This could improve consistency in how patients are treated, for example, by determining who is able to have surgery.
Our researchers are also looking at how best to deliver chemotherapy. Currently, chemotherapy is usually delivered through a drip into the blood stream, which means that it often damages healthy cells all around the body, leading to significant side effects.
With your support, we’re investigating how to deliver chemotherapy in a more targeted way. We funded Dr George Williams at the University of Southampton to develop a new drug delivery system which uses molecules called prodrugs. These prodrugs hold chemotherapy drugs in an inactive form until they reach the tumour, where they become active. Dr Williams developed prodrugs for pancreatic cancer which can successfully deliver drugs into tumours. He has now secured additional funding to explore this further.
Sadly, even after surgery, pancreatic cancer recurs in over 75% of patients, often due to undetectable cancer cells remaining in the pancreas. We funded Professor Christopher McConville at the University of Birmingham to develop a device called the ChemoPatch to deliver chemotherapy directly to the pancreas. The ChemoPatch device is implanted following the operation, allowing chemotherapy to be delivered directly to the right area of the body. Our funding enabled Professor McConville and his team to improve the design of the ChemoPatch device, and they have now had interest from a company to develop the device further.
Our researchers have also explored the best way to use neoadjuvant treatment. This is treatment that patients receive before surgery (for example, chemotherapy or radiotherapy) with the aim to try and reduce the size of the tumour and improve the chances of a successful surgery.
A large proportion of cells in pancreatic tumours are actually normal cells that have been ‘hijacked’ by the cancerous cells so that they help support and protect them. Some studies have shown that radiotherapy can make the normal cells more helpful to the cancer cells, and therefore having radiotherapy before surgery may help the tumour grow, rather than shrink it.
Professor Jen Morton and her team at the University of Glasgow explored the effect of radiotherapy on these normal cells with the aim of identifying how to prevent radiotherapy from helping the tumour. They found that radiation therapy initially increased the number of immune cells in pancreatic tumours, as well as proteins that cause inflammation. However, within three weeks, the levels of these cells and proteins had returned to those seen in the tumour before radiation, and the immune cells appeared to have a reduced capacity to attack the cancer cells. These findings suggest that a combination of immunotherapy and radiotherapy could potentially be used to boost the immune system in the tumour. Professor Morton has been awarded over £2 million from the Medical Research Council to build upon this work and investigate whether combining radiotherapy with other treatments could make be more effective.
Supportive care
Supportive care aims to help people with pancreatic cancer to live as well as possible for as long as possible. It may involve preventing and managing symptoms, treatment side effects, and the impact a serious illness can have on someone’s mental health. Our researchers are working hard to improve supportive care for people with pancreatic cancer across the UK.
Pancreatic enzyme insufficiency (PEI) occurs when the pancreas becomes unable to produce enough enzymes to break down food, and in effect causes the body to starve. The condition affects 60-90% of people with pancreatic cancer and has unpleasant effects. It reduces quality of life, and causes symptoms such as extreme weight loss, malnutrition, pain and diarrhoea. PEI can be treated with simple tablets called Pancreatic Enzyme Replacement Therapy (PERT), which replace those enzymes so that food can be digested again. However, just half of people with pancreatic cancer are prescribed the medicine in the UK, in part due to GPs not having the right tools to diagnose PEI quickly or accurately.
The current diagnostic stool test for PEI is not very accurate and takes a long time to process, often leading to delays in prescribing PERT, missed diagnoses and insufficient treatment. Professor Keith Roberts and Dr Sarah Powell-Brett from the University of Birmingham identified a group of biomarkers in the blood that can be used to clearly identify people with PEI. Further work is now required to develop a blood test based on these biomarkers. If successful, this test could help ensure early diagnosis of PEI, appropriate enzyme therapy, and better management of symptoms. Ultimately, it could also improve patient quality of life and survival rates.
People with pancreatic cancer frequently have ongoing physical and psychological needs both during and after treatment, many of which are not met by existing healthcare and supportive care services. Family members often step into this gap to which can take a significant toll of carers. Professor Sanjay Pandanaboyana from Newcastle University investigated the impact of pancreatic cancer on caregivers. His research shed new light on the roles carers take on, as well as their unmet needs, and identified areas where support is most needed. These findings could, in future, lead to more tailored support services, clearer communication and better integration between hospital and community care. In the long term, addressing these gaps could hold improve outcomes for both patients and carers.
Your support is helping us to treat better
Thanks to your generous support, our researchers are pushing the boundaries of what’s possible. Together, we’ve funded research that has already made progress in developing and discovering new treatments for pancreatic cancer, as well as making current treatments more effective. This research will help people with pancreatic live well for longer and have more precious time with their loved ones. Thank you so much – we couldn’t do this without you.
