Pancreatic cancer is actually four different diseases

An international research team has discovered that pancreatic cancer is actually four separate diseases with different genetic triggers and survival rates. Researchers hope that the new reclassification will help to identify the correct targeted treatment for each individual subtype of the disease.

Pancreatic cancer patients have a poor prognosis, with a median survival measured in months and a five-year survival rate of less than 5%. Only a small number of patients can have their tumour affected by treatment, as current methods are not targeted or selective.

The study authors carried out comprehensive genomic analysis on 456 pancreatic cancers, taken from participants recruited through the Australian Pancreatic Cancer Genome Initiative (APGI), to determine the core processes that are damaged when normal pancreatic tissues change into aggressive cancers. They combined the results of several techniques to examine not only the genetic code, but also variations in structure and gene activity, revealing more information than ever before about the genetic damage that leads to pancreatic cancer.

“We identified 32 genes from 10 genetic pathways that are consistently mutated in pancreatic tumours, but further analysis of gene activity revealed four distinct subtypes of tumours,” said study leader Professor Sean Grimmond, formerly of The University of Queensland’s Institute for Molecular Bioscience (IMB) and now the director of research at the University of Melbourne Centre for Cancer Research.

“This study demonstrates that pancreatic cancer is better considered as four separate diseases, with different survival rates, treatments and underlying genetics.”

The research paper, published in the journal Nature, has named the four subtypes as follows:

• 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.
• 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.
• Aberrantly differentiated endocrine exocrine (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.

“We have previously shown that pancreatic cancer is not one disease but several — but now we have identified distinct subgroups in detail, along with the genetic drivers that underpin them,” said Amber Johns from APGI.

“This research is critical to the development of precision medicine for pancreatic cancer — essentially, it has the potential to take the guesswork out and make it possible to customise treatment approaches for individual patients.

“For APGI, the challenge now is to develop strategies to apply these findings in real-life clinical settings. We are working actively on ways to use big datasets, such as one highlighted in this paper, to improve outcomes for patients with pancreatic cancer.”

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