This project focuses in the mapping and targeting the extracellular matrix (the surrounding area of the tumour) in pancreatic cancer. A cancer cell’s surroundings significantly impact on disease progression. Prof. Paul Timpson’s team has devised a new way to dissolve cells from tumours, leaving behind the delicate 3D-architecture of the matrix to allow the group to study and tap into the vast and currently unexplored reservoir of anti-cancer matrix targets in this disease.

The Pajic team has demonstrated that a novel Wnt pathway inhibitor favourably alters pancreatic cancer biology, making tumours more susceptible to current standard of care chemotherapy and potentially immunotherapy. The Wnt pathway has been implicated in pancreatic cancer driving progression, proliferation, and survival of cancer cells, furthermore, dysregulation of Wnt has been shown to result in drug resistance in pancreatic cancer. Results from this study will provide vital pre-clinical efficacy data to inform clinical translation of Wnt pathway inhibitors in combination with chemotherapy against this devastating disease.

For a patient diagnosed with pancreatic cancer, their immediate future is often filled with anxiety and uncertainty. Pancreatic cancer patients also experience high levels of pain and the patient’s quality of life becomes very bleak causing distress to patients and their families. Scientists know that the pain is associated with “perineural invasion” where the cancer cells invade the nerves in the pancreas causing pain and nerve invasion is also a path for cancer cells to spread to other organs. But the mechanisms involved in the cancer invasion of nerves is not completely understood. This project uses cutting edge technology that allows the scientists to study at a microscopic level how the cancer, nerve and immune cells interact in their microenvironment in the pancreatic tissue. This project has the potential to identify mechanisms that could targeted to stop cancer invading the nerves reducing pain and stopping the disease from spreading.

This team has demonstrated that a therapeutic strategy involving itraconazole and current standard-of-care chemotherapy Gemcitabine/Abraxane is very effective in pancreatic tumours. This project will investigate what proportion of patients characterised by these markers may potentially benefit from this new combination treatment strategy.

The Hooper team prose to develop new antibody-based agents against two cell surface proteins for detection and treatment of pancreatic cancer. The agents contain two components, a biological component, called an antibody, that binds strongly to proteins enriched on the surface of cancer cells; and a  ‘payload” this is linked to the antibody and either emits energy (for tumour detection) or is a drug (for treatment). The agent binds to the protein thereby precisely delivering its payload to cancer cells. We propose to simultaneously target two different proteins so that our approach will be more sensitive than current approaches at detecting and treating pancreatic cancer. The group also propose to study two other key proteins in pancreatic cancer which either control how cancer cells grow and divide or help cancer cells tolerate chemotherapies. The team’s focus is understanding how these proteins function in pancreatic cancer and how their function can be blocked.

Even in those who undergo regular testing for pancreatic cancer, this terrible disease is usually incurable by the time it is discovered. PET imaging is an exciting and rapidly progressing area of medicine where small deposits of cancer may be detected early. This type of imaging relies on injecting a “tracer” into the blood stream which targets the cancer tissue. To use this technology to diagnose pancreatic cancer early, the tracers that target the disease in its earliest stages must be figured out. This project will use a large array of samples of pre-cancerous and cancerous pancreatic lesions to determine the targetability of two promising new PET tracers. This will guide extremely important research into how PET scans might be used to diagnose early pancreatic cancer, particularly in high-risk individuals undergoing regular testing.

Ampullary adenocarcinoma is a heterogeneous disease with an unclear benefit of adjuvant chemotherapy post-surgery. This group previously identified a molecular classifier that was able to quantify the genomic heterogeneity in ampullary adenocarcinoma specimens and provide a prognostic subtype that outperformed standard classification for predicting long-term survival.  Further research can determine whether genomic classifiers is a predictive biomarker and not merely a prognostic biomarker – to guide use and type of adjuvant chemotherapy in order to improve the long-term survival of ampullary cancer patients.

Cancer is a disease of faulty genes. One particular class of pancreatic cancers is characterised by mutations in a gene called BRCA1, or in similar, so called ‘BRCAness’ genes. Though there are approved drugs for this type of pancreatic cancer, cure is rarely achieved. Up to 90% of pancreatic tumours consist of ‘normal’ cells like wound healing cells and immune cells, which help support the tumour. This team have found that the composition, the number and the functions of these ‘normal’ cells in the tumour differ between tumours with the BRCA1 mutations or BRCAness. By using drugs which target the ‘normal’ cells, the team have successfully refined treatments in their preclinical models. This research project aims to further identify whether the preclinical findings can be reproduced using human tissue in order to inform clinical trials and improve treatment outcomes for patients with this type of cancer.

Pancreatic ductal adenocarcinoma is a lethal cancer disease, develops predominantly through distinct precursor lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). While progression of PanIN into invasive cancer has been well characterised, there is an urgent need to understand the biology of IPMNs. IPMNs present a unique clinical challenge, as they are very frequent and incidentally found in about 13% of subjects who undergo routine abdominal imaging studies. This study will identify and validate biomarkers responsible for degeneration of IPMN and the early metastatic dissemination of IPMN-derived pancreatic ductal adenocarcinoma in order to stratify IPMN patients to different therapeutic interventions.