Identification of four Pancreatic Cancer subtypes offers new treatment insight into the disease

Researchers at the University of Glasgow are part of an international team that have discovered that pancreatic cancer can be divided into four key subtypes which presents new opportunities to treat the disease.

The study, co-led by Professor Andrew Biankin and a team from the Wolfson Wohl Cancer Research Centre at the University of Glasgow shows that each subtype has its own distinct clinical characteristics and differential survival outcomes. The research paper, which is published today in Nature, has named the four subtypes as Squamous, Pancreatic Progenitor, Immunogenic and ADEX (Aberrantly Differentiated Endocrine eXocrine).

The groups were categorised based on data sets from the Australian Pancreatic Cancer Genome Initiative, after examining key aspects of pancreatic tumours including their mutational profile, the expression of genes and epigenetic changes.

Currently those suffering with pancreatic cancer have a poor prognosis, with a median survival measured in months and a five year survival rate of less than 5%. The disease progresses “silently” within the pancreas for up to 15 to 20 years, until patients present to the clinic when they are in the later stages of the disease. From those who are diagnosed with the disease only a small number can have their tumour affected by treatment.

The current methods of treating pancreatic cancer are not targeted or selective and have been described as “hitting the disease with a mallet with your eye closed”. Researchers hope that the new reclassification will help to identify the correct targeted treatment for each individual subtype of the disease.

Professor Biankin, the Regius Chair of Surgery/Director of the Wolfson Wohl Cancer Research Centre, said: “There is an urgent need to better understand the molecular pathology of Pancreatic Cancer in order to improve patient selection for current treatment options, and to develop novel therapeutic strategies.

“The four subtypes that we have identified represent a reclassification of the disease and as such should provide a basis to offer new insights into personalised therapeutic options for individual patients and a launch pad to investigate new treatments.”

The study also found that the four key subtypes matched with known pancreatic cancer histopathology.

Details of the four subtypes included:

• Squamous: Many of the genes associated with this subtype are highly expressed in molecular “Squamous-type” tumours that also appear to occur in breast, bladder, lung and head and neck cancer.
• Pancreatic Progenitor: Gene networks that regulate the early embryonic development of the pancreas characterise this subgroup.
• ADEX: This class is defined by transcriptional networks that are important in later stages of pancreatic development and differentiation, and is a subclass of Pancreatic Progenitor tumours.
• Immunogenic: This class shares many of the characteristics of the Pancreatic Progenitor class but is associated with evidence of a significant immune infiltrate. The study found inferred therapeutic opportunities in this class.

One of the key findings of the report was the identification of the Immunogenic subtype, which the study found could potentially prove to be responsive to types of immunotherapeutic cancer treatments.

Professor Biankin said: “The novel immunogenic subtype of pancreatic cancer is characterised by specific mechanisms that can potentially be targeted using immune modulators, and testing in clinical trials is encouraged.”

Dr Peter Bailey, the first author of the study, said: “The standard of care for Pancreatic Cancer really hasn’t changed in the last 20 years. There are a number of different chem therapeutic options but in general it’s not very selective – it’s like hitting the disease with a mallet with your eyes closed.

“The work that we are doing is about trying to change the clinical landscape for, not only pancreatic cancer, but all cancers by providing a very thorough analysis of the molecular pathology of specific cancers, leading to a more personalised or precise approach to treatment based on the underlying genetic defects that drive a cancer that may be vulnerable to specific drugs”

The data for the study came from the Australian Pancreatic Cancer Genome Initiative and the Queensland Centre of Medical Genomics.

Dr Emma Smith, senior science information officer at Cancer Research UK, said: “Identifying different types of pancreatic cancer and revealing the disease’s complexity is an important step towards finding more effective treatments. This will help to ensure patients are given the therapies that are most likely to help. Improving survival for people with pancreatic cancer is one of our top priorities, and we urgently need more research like this if we’re going to beat this disease in the future.”

Pancreatic Cancer UK is supporting Andrew Biankin’s research into the area of personalised medicine through its Future Leaders Fund. Leanne Reynolds, the charity’s Head of Research, said: “The findings of this research are incredibly exciting for anyone affected by pancreatic cancer, as they should mean that in the future the right patients can be given the right treatment at the right time. This is crucial for people with pancreatic cancer, because the disease is difficult to diagnose, is often diagnosed terribly late, and just four per cent of people live for five years or more after diagnosis. If we can predict more accurately which treatment would be most effective for each patient, we can ensure patients have the best chance of living for as long as possible, as well as possible. We are proud to support Andrew Biankin and his team as they aim to transform the future for people with this disease.”