Early detection of pancreatic cancer

Background

Pancreatic cancer is a devastating disease with very poor outcomes and only 7.3% of people survive this cancer for 5 years or longer in England (Cancer Research UK). In contrast to many other cancers, pancreatic cancer survival has shown little improvement over the past 40 years. The majority (nearly 70%) of patients with pancreatic cancer are diagnosed at stage 4, which is frequently too late for potentially curable treatment to be applied. There is an urgent need to detect pancreatic cancers earlier with the aim of improving outcomes from this disease.

There are several projects underway in Oxford that are looking for new strategies to detect pancreatic cancer earlier.

Using patient and biobank data to identify risk factors and symptoms for pancreatic cancer

Since there are currently no reliable screening tests for pancreatic cancer in asymptomatic individuals, nearly all pancreatic cancers are diagnosed in people experiencing symptoms. However, these symptoms are frequently vague and not specific for pancreatic cancer. Gains in earlier diagnosis can therefore be made by improving risk assessment tools for GPs to prompt further investigation of patients with concerning symptoms.

Professor Julia Hippisley-Cox, Dr Weiqi Liao (Nuffield Department of Primary Care Health Sciences) and co-workers are undertaking research using the QResearch database of over 35 million anonymised patient health records. As part of the ADEPTS study led by Professor Stephen Pereira (University College London), they are identifying a series of symptoms associated with pancreatic cancer (including pancreatic ductal adenocarcinoma and pancreatic neuroendocrine neoplasm) and plan to update the QCancer (Pancreas) risk prediction tool to promote earlier diagnosis of pancreatic cancer.

Using a similar approach, Julia's team is developing and validating a risk assessment tool for early diagnosis of pancreatic cancer among individuals with new-onset diabetes. Roughly a quarter of patients diagnosed with pancreatic cancer have a prior diagnosis of type-2 diabetes and, in the longer term, it is hoped that a risk assessment tool would help GPs to prioritise patients for further investigation.

Oxford researchers are also working with data from over 500,000 adults in the China Kadoorie Biobank to identify risk factors and blood test biomarkers for pancreatic cancer. Dr Christiana Kartsonaki, Associate Professor Michael Holmes, Professor Zhengming Chen, and Dr Yuanjie Pang (Nuffield Department of Population Health) have identified links between diet, alcohol, smoking and pancreatic cancer and, separately, diabetes, plasma glucose and pancreatic cancer in this population. The team are also analysing blood test results from people within the biobank to identify protein or metabolite biomarkers for pancreatic cancer.

Developing blood tests for detecting pancreatic cancer

A simple, minimally invasive test such as a blood test to look for indicators of pancreatic cancer in people soon after they experience potential pancreatic cancer symptoms is an attractive strategy for ruling people in or out of further, more expensive and resource-intensive tests to enable earlier detection. The blood-borne indicators currently under investigation in Oxford include circulating cancer DNA, exosomes and tumour-educated platelets.

DNA-based cancer detection tests

Blood contains small fragments of DNA that have been released into the bloodstream from many parts of the body, including tumours. DNA from cancer cells has subtle differences compared to DNA from healthy cells. In Oxford, we have a couple of research projects underway to develop new methods for detecting pancreatic cancer-derived DNA in the blood.

Dr Siim Pauklin (Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences) is working to identify a pancreatic cancer-specific DNA signature. In the long-term, it is hoped that this can be used as the basis of a simple blood test to detect the presence of pancreatic cancer earlier.

Dr Chunxiao Song (Ludwig Institute for Cancer Research, Oxford) is collaborating with Dr Shivan Sivakumar (Department of Oncology and Oxford University Hospitals Foundation NHS Trust) to apply his TAPS technology to pancreatic cancer. TAPS is a new, more sensitive method for detecting methylation on DNA, allowing analysis of the very small levels of circulating tumour DNA in the blood. The team are working to identify patterns of DNA methylation that are specific for pancreatic cancer and able to accurately distinguish it from other non-cancerous pancreatic disorders such as pancreatitis.

Investigating exosomes for pancreatic cancer detection

Exosomes are tiny membrane-bound spheres containing a variety of biomolecules that are released by cells as a way of communicating with each other. Exosomes are found in almost all body fluids, including blood. There is high diversity between exosomes and a research project led by Dr Siim Pauklin and supported by the OxCODE Funding Scheme aims to identify cancer-specific and tissue-specific exosome biomarkers to enable the identification of pancreatic cancer-derived exosomes in the blood.

Cancer detection using tumour-educated platelets

Platelets perfuse tumours and take up cancer cell-derived biomolecules. Dr Bethan Psaila (Medical Research Council Weatherall Institute of Molecular Medicine and Radcliffe Department of Medicine) is investigating whether isolating platelets from the blood and analysing their contents is a sensitive method for detecting cancer-specific molecules. Led by Bethan, the project will assess the utility of ‘tumour-educated’ platelets (TEPs) for early diagnosis of several types of cancer, including pancreatic cancer.

Developing A New sensor device for detecting the malignant transformation of pancreatic cysts

Pancreatic cysts are are fluid-filled sacs on or in the pancreas. While these are mostly benign, 2-3% are precancerous and can develop into pancreatic cancer. Cysts are often identified incidentally and are then monitored for malignant transformation, but early cancers are still being missed since current methods have limited sensitivity and specificity. A team including Oxford’s Professor Eric O’Neill (Department of Oncology) aims to develop a new real-time highly sensitive sensor device to detect malignant transformation in people with pancreatic cysts. Optrodes - optical sensor devices that detect light emitted as a result of an electrochemical reaction - will be used to detect cancer biomarkers in cyst fluid.

These projects, together with others in development, are aiming to achieve earlier detection of pancreatic cancer which, in combination with the development of new treatments by other researchers within Oxford Cancer, will hopefully improve the outcomes of patients with this disease.

The work described on this page has received funding from: