Researchers: Professor Nicholas Lemoine, Barts and the London, Professor John Neoptolemos, Royal Liverpool University Hospital

Programme Grant

Grant Total: £500,000

Can a cold-virus cure cancer of the pancreas? Professor Nick Lemoine and his research team think it can. They have engineered a cold virus that targets cancer cells in the pancreas and grows so quickly that it makes the cancer cells burst and die. Unlike other anti-cancer drugs, the only side effects will be some flu-like symptoms.
Cancer of the pancreas is the fifth most common cause of cancer death in the UK. By the time most patients are diagnosed their disease is too advanced to permit surgical removal of the tumour. Even when an operation is possible patients are often offered chemotherapy and radiotherapy as well, although this type of cancer is usually resistant to these treatments. A radical change in pancreatic cancer treatment is needed if the outlook for patients is to improve. This change itself must be based on a deep understanding of the genes that drive the disease. The proposal is to use the genes themselves as targets for therapy.

The research team has developed methods of identifying the genes responsible for causing pancreatic cancer. The plan is to attack these genes with a modified version of the common cold virus. This virus has characteristics which, they believe, might destroy the genes driving the growth of the tumour - thereby stopping the spread of the cancer. The immediate aim is to take this research forward to the stage of clinical trials.
If successful this research will produce novel treatments that should significantly increase the chances of survival in patients with pancreatic cancer.

Progress Report

Early Diagnosis

One of the serious problems in treating patients with pancreatic cancer, is that the disease is often very difficult to diagnose, and by the time symptoms develop, the cancer has already spread, making treatment very much more difficult. Early diagnosis of pancreatic cancer could have a significant impact on improving survival rates and this piece of work was designed to try and find markers in pancreatic tissue to differentiate among pancreatic cancer, chronic pancreatitis, and normal pancreas.

Analysis of more than 900 well-characterized antibodies was performed with tissue specimens from patients with chronic pancreatitis, pancreatic cancer, and normal pancreas.

The analysis showed significant changes when normal pancreas tissue was compared with chronic pancreatitis and pancreatic cancer. Although a substantial proportion of similar changes were found in both chronic pancreatitis and pancreatic cancer, several proteins were identified as potential disease-specific markers.

A large number of proteins are differentially expressed in chronic pancreatitis and pancreatic cancer compared with normal pancreas. This work has shown that among these, some could potentially provide a useful additional diagnostic tool during clinical examination and investigations.

Biological therapy for pancreatic cancer

The research team has continued to make good progress in the development of a new class of biological therapy, so-called oncolytic virotherapy which is based on the ability of certain modified viruses to destroy cancer cells selectively. The viruses they have constructed are derived from a type of virus called Adenovirus, which in nature causes a flu-like illness but in the form developed by the research team, has the special property of multiplying and spreading through cancer tissues only.

The identification of potential biomarkers for chemoresistance/sensitivity has afforded the opportunity to incorporate these in to “molecular checklists” for patient selection in future clinical trials with combined chemotherapeutics. This is being explored through the European Pancreatic Cancer Clinical Trials Steering Committee on which both principal investigators sit. The novel oncolytic viruses under construction represent a novel class of anti-cancer agent, and the ultimate aim of the Core programme is to see them through to clinical trial in patients with pancreatic cancer.