INvestigating the Source of volatile organic compounds in Pancreatic ductal adenocarcinoma using cancer-associated fIbroblast-oRganoid co-culturEs

Research context:

Unlike other cancer types, which have recently seen significant improvements in their treatments and survival, pancreatic cancer continues to have extremely poor patient outcomes. Less than ten percent of patients diagnosed with pancreatic cancer survive more than five years after diagnosis. A major contributing factor is that pancreatic cancer is often detected at an advanced (incurable) stage.

In the United Kingdom, nearly half of patients have Stage 4 disease at the time of diagnosis, which has a profound effect on treatment options and, ultimately, survival.

Improving early detection of cancer is essential for improving survival, by providing patients with a window of opportunity to undergo treatment with curative intent. However, diagnosing pancreatic cancer at an early stage remains a challenge, as the signs and symptoms of early pancreatic cancer are often similar to those of many common illnesses. This makes it hard for doctors to identify which patients should be tested for pancreatic cancer.

One solution for improving early detection of pancreatic cancer, being developed by our laboratory, is a simple breath test that detects small molecules, called volatile organic compounds (VOCs), which are different in the breath of patients with and without pancreatic cancer. This breath test could be offered to patients visiting a General Practitioner with non-specific symptoms, which for many patients will be due to one of a number of common illnesses, but in a minority may be due to undiagnosed pancreatic cancer.

Challenge this project addresses:

An important aspect in developing this breath test is to identify how the breath VOCs that are used to detect pancreatic cancer are produced within the cancer environment. This project aims to address this by studying VOC production from pancreatic cancer using a laboratory model. This will help us to identify specific VOCs produced from pancreatic cancer, even when occurring at very low concentrations in breath, thus making the breath test more accurate.

To ensure the model is as representative of pancreatic cancer as possible, it will contain both cancer cells and the surrounding cells that are known to promote the growth and spread of these cancers. This allows the model to resemble more closely the interactions occurring between these cells in the human body, which may influence VOC production.

Overall aim:

To study VOC production from pancreatic cancer using a laboratory model. This model will use cells from 15 human pancreatic cancer samples and 5 normal human pancreas samples that are grown as groups of cells (organoids), as well as their surrounding supporting cells (cancer-associated fibroblasts) to mirror their interactions in the human body. This project will be based at Imperial College, with additional work taking place at the Cancer Research UK Convergence Science Centre.

Objectives: To identify pancreatic cancer specific VOCs, compared with normal pancreas VOCs, using groups of pancreatic cells.

To grow groups of pancreatic cancer cells together with supporting cells found inside the pancreatic cancer environment, to see whether this affects overall VOC production. To use the above laboratory model to identify biological pathways contributing to VOC production in pancreatic cancer. Potential applications and benefits:

Alongside the results of parallel clinical studies, this research will support a future breath test that will offer an opportunity to improve earlier detection of pancreatic cancer, with benefits to both patients and the health service.