Pancreatic cancer is the tenth most common cancer in the UK, with around 10,500 people diagnosed every year. This cancer has some of the lowest survival rates and is the fifth biggest cancer killer.

In the early stages, symptoms of pancreatic cancer are vague. Often, the first signs are general back and abdominal pain, which results from tumours invading the nerves of the pancreas. However, with so many non-critical causes of abdominal pain, it can be difficult to distinguish pancreatic cancer from other more common ailments.

While many scientists are exploring early tumour detection, researchers in the Department of Life Sciences want to find out more about how pancreatic cancer grows, and exactly what happens when the tumours interact with nerve cells.

Growing our understanding

As tumours develop, they grow into the nerves that connect to the pancreas. Nerves carry different types of information to the tumour cells, and it's the growth of tumours into sensory nerves that is associated with this cancer pain.

One way of studying the interactions between tumour cells and nerves is by generating a model tumour in the laboratory that incorporates both.

With this approach, Dr Ed Carter and his team can see how tumour cells behave and interact with nerves in a laboratory setting, rather than in humans or animals. This allows the team to carry out much more controlled investigations into how nerves can promote tumour growth, and how tumours stimulate nerve activity to cause pain.

Previously, researchers have conducted their experiments by taking nerve cells from mice and introducing them to human tumour cells.

Recent advancements in stem cell research now allow the team to use nerve cells grown from human stem cells. Stem cells are specialised cells that can turn into any cell type in the body. By carefully controlling their growth, the team can make human sensory neurons for their tumour model. When placed together with tumour cells, they can see how the tumour cells affect growth, signalling, and activity in those nerves.

‘It’s now appreciated that the nerves in the pancreas help the tumour grow and spread,’ explains Ed. ‘We’re looking to understand how and why this happens so we can explore new treatment options. If we can also understand how tumour cells modulate and activate nerves, we can identify more effective therapies for pain relief and improve patients’ quality of life.’

Building a model tumour

While animals make good model systems and are instrumental in assessing new therapies, using a human model grown in the laboratory allows researchers to see how cells in a human system behave, helping to ensure that any drug target is relevant to human disease.

Mini tumours derived from donated patient tissue, termed ‘organoids’, can be cultivated in the lab and show remarkable similarity to the original tumour. When mixed with human nerves, they grow together and allow Ed and his team to study the tumour-nerve interactions in a model that reflects the biology within a patient's tumour.

To verify that model tumours behave the same as in the human body, any findings the team identify in the lab must also be clear in patients. For example, if the team's model system activated a particular pain pathway, they must also look in patients with pancreatic cancer to check if the same pain pathway is activated. Together, this will provide strong patient-based evidence for a potential drug candidate before taking it forward to animal models as a prelude to clinical trials.

Taking the next steps

Although still in the early stages, the models are almost developed, and the team is beginning to get a clearer understanding of the molecular machinery inside tumours. When the models are ready, the team will be able to look at different aspects of the disease and different factors affecting its progression.

One advantage of using this organoid approach to studying nerve and tumour interactions is the ability to study a range of biological factors that may influence tumour development and pain. For example, there may be sex differences in how nerve cells interact with tumours. Researchers can use tumour samples or stem cell-derived nerves from females or males in these models.

Their findings may even help our understanding or treatment of tumour-nerve interactions in other cancers, like prostate cancer or bone metastasis.

Once the team understand the key mechanisms between nerve and cancer cells, they hope to identify new drug targets or repurpose already available drugs to reduce pain and improve quality of life for pancreatic cancer patients.