25th February 2016

Pancreatic cancer breakthrough: four subtypes identified

Pancreatic cancer has been found to have four separate subtypes, each with a different cause and requiring a different treatment.

An international team led by Australian researchers has studied the genetics of pancreatic cancer, revealing it is actually four separate diseases each with different genetic triggers and survival rates, paving the way for more accurate diagnoses and treatments.

These major findings also include 10 genetic pathways at the core of transforming normal pancreatic tissue into cancerous tumours. Some of these processes are related to bladder and lung cancers – opening up the possibility of using treatments for these cancers to also treat pancreatic cancer.

The study, led by Prof Sean Grimmond at the University of Melbourne Centre for Cancer Research, was published yesterday in Nature. Over seven years, his team analysed the genomes of 456 pancreatic tumours to find the core processes that are damaged when normal pancreatic tissues change into aggressive cancers.

Professor Grimmond said there was an urgent need for more knowledge about the genetic causes of pancreatic cancer, given its very low survival rate with most patients only living a few months after diagnosis – and the condition is predicted to become the second most common cancer in Western countries by 2025.

"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 Prof. Grimmond. "This study demonstrates that pancreatic cancer is better considered as four separate diseases, with different survival rates, treatments and underlying genetics. Knowing which subtype a patient has would allow a doctor to provide a more accurate prognosis and treatment recommendations."

Importantly, Prof. Grimmond said there are already cancer drugs, and drugs in development, that can potentially target parts of the 'damaged machinery' driving pancreatic cancers to start. For example, some strains of pancreatic cancer are unexpectedly associated with mutations normally associated with colon cancer or leukaemia and for which experimental drugs are available or in development. Other pancreatic cancers bear strong similarities to some bladder and lung cancers and researchers can now start to draw on that knowledge to improve treatments.

In a world first, his team performed an integrated genomic analysis – meaning they combined 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.

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