Translational Research > Pancreatic Cancer

Pancreatitis affects around 6,000 patients per year in the UK and leads to death in around 1 in 10 cases. Little is known about the mechanisms of the disease. Treatment is still in state of evolution and in particular little is known about modifying the disease in individuals affected with inherited pancreatitis. We are at the forefront of identifying the underlying mechanisms and developing new means of treatment for pancreatitis.

What is also worrying is the greatly increased risk of pancreatic cancer in those individuals that suffer from chronic pancreatitis. Just how pancreatic cancer is linked to chronic pancreatitis is also under detailed investigation by our research groups.

No one group or university can hope to combat these diseases working alone. We work as part of the MRC co-operative on gastrointestinal diseases within Liverpool and part of the EU funded PACA consortium in a wider context. Other national and international collaborations are described below and on individual research pages.

1. Clinical trials aimed at determining the overall benefits of current treatments and evaluating the benefits of newly emerging treatments for pancreatic cancer.

The Division of Surgery and Oncology is the centre for large European pancreas studies including the ESPAC clinical trials aimed at examining the benefit of chemotherapy and chemoradiotherapy (the combined use of chemotherapy and radiotherapy) in the treatment of patients who have undergone surgery to remove pancreas cancer tissue.
There are major clinical trials in advanced pancreatic cancer (such as Gem-Cap) and developmental trials focusing on new biological agents such as the use of targeted super-antibodies and gene therapy.
 
In the palliative care setting we are at the forefront of assessing and optimising novel methods of symptom and pain control.These and other trials that are available to patients at Liverpool will hopefully improve our understanding of the currently available treatments for pancreas cancer.

2. Development and Co-ordination of the world's largest collection of families with Hereditary Pancreatitis and Familial Pancreas Cancer.
 
The Division of Surgery and Oncology also co-ordinates the EUROPAC register which is the world's largest collection of families with Hereditary Pancreatitis and Familial Pancreas Cancer.
 
Researchers in the Division are currently working with these families to identify the underlying genetic cause of cancer in patients where the disease is inherited.
This research also allows us to offer individuals on the register the most advanced screening for what may be early signs of pancreatic cancer. We are constantly working to improve the methods by which we carry out the screening, in the hope that one-day it will advance to the point where potentially lifesaving screens can be offered to a wider range of people.
In young patients with Hereditary Pancreatitis and Idiopathic Pancreatitis we are trialling novel treatments to inhibit or minimize the frequency or severity of the attacks (Europac 2).
  
3. Identification of novel drug targets or diagnostic markers for pancreatic cancer.

In an attempt to identify suitable drug targets or diagnostic markers for pancreatic adenocarcinoma, we have begun a systematic comparison of protein expression profiles from highly purified specimens of pancreatic adenocarcinoma and corresponding normal tissue.
We have established the feasibility of the approach of purification of normal and cancer cells of pancreas by laser capture microdissection followed by visualisation of proteins by two dimensional gel electrophoresis and have identified several proteins whose expression is abnormally high or abnormally low in pancreatic cancer cells. Validation and follow-up of these proteins is ongoing.
  
4. Increasing the efficacy of currently used chemotherapeutic drugs for treating pancreatic cancer.

Given the chemo-resistant nature of pancreatic cancer, we are investigating whether combining chemotherapy with other forms of therapy will more potently kill pancreatic cancer cells. We grow pancreatic cancer cells in the laboratory and investigate what factors make them more susceptible to drugs that could be offered to patients. In this way novel combinations of drugs have been identified which are more effective than the drugs used separately, for example inhibitors of the protein Hsp90 increase the sensitivity of the cancer cells to the commonly used chemotherapeutic 5-fluorouracil.

We are also looking at the genetic changes in cancer cells that determine sensitivity to drugs. The gene p16Ink4a is mutated in most pancreatic cancer cells. This gene is a tumour suppressor gene (it normally acts to prevent cancer). We can replace the defective gene in the cancer cells with a healthy form and we have shown that this dramatically increases the potency of the 5-fluorouracil.

In parallel with this we are working on identifying novel tumour suppressors (such as the gene MTBP) and on a novel type of therapeutic gene delivery tool, the lentiviral vector, which could be used to deliver beneficial genes such as p16Ink4a to cancer cells in patients.

With our very close collaborators in the Department of Physiology (University of Liverpool) we are one of the world's leading research centres that is unravelling the mechanisms and consequences of pancreatitis from the sub-microscopic level to the whole patient.

Our Centre is the UK's largest Pancreas Treatment Centre offering and developing the latest clinical treatments for pancreatic cancer, acute pancreatitis and chronic pancreatitis and is one of the world's leading Pancreas Research Centres.

A vital part of our research is dependent on philanthropic donations especially from patients, relatives and friends. Every donation, however small is spent directly on pancreas research or treatment.

The international standing of our research can be judged from the continued support that we have from recognized major research funding bodies from the UK and Europe.
Our research funding sources include the Medical Research Council, Cancer Research UK, Pancreatic Cancer Research Fund, Biotechnology and Biological Sciences Research Council, Digestive Diseases Foundation, North West Cancer Research Fund, The Association of International Cancer Research, Augustus Newmam Foundation, Royal Liverpool University Hospital Research and Development, NHS Executive Research and Development and the European Union.

Groups specialising in this field:
Professor John Neoptolemos		Professor Daniel Palmer		Professor Paula Ghaneh		Dr Eithne Costello-Goldring		Dr Bill Greenhalf