After carrying out a detailed analysis of DNA disruption, gene expression and molecular pathways in hundreds of tumors, researchers conclude pancreatic cancer is not one but four separate diseases, each with a different genetic trigger and requiring a different treatment.
The researchers say knowing which subtypes of pancreatic cancer a patient has will allow doctors to give more accurate prognoses and treatment recommendations.
The results also raise the possibility that some types of pancreatic cancer may be treatable with drugs already in use for other cancers with similar underlying genetics.
In the journal Nature, the international team – led by Prof. Sean Grimmond of the University of Melbourne in Australia – describes how they classified pancreatic cancer into the following four subtypes:
- Pancreatic progenitor
- Aberrantly differentiated endocrine eXocrine (ADEX).
Prof. Grimmond, who also leads research based at the University of Glasgow in the UK, explains:
“We identified 32 genes from 10 genetic pathways that are consistently mutated in pancreatic tumors, but further analysis of gene activity revealed four distinct subtypes of tumors.”
He and his colleagues say each subtype of pancreatic cancer has different survival rates, treatments and underlying genetics.
The study addresses an urgent need to improve our understanding of the causes of pancreatic cancer – particularly at the genetic and molecular level.
Most patients with pancreatic cancer only live a few months after diagnosis and the disease is set to become the second most common cancer in westernized countries in the next 10 years.
For the study, the team analyzed the genomes of 456 pancreatic tumors to identify the underlying genetic and molecular processes that go wrong inside cells when normal pancreatic tissue changes into aggressive cancer.
Cancer arises when normal cells go wrong – for example, a DNA copying error when cells divide can lead to damage inside the cell machinery. This error or mutation propagates in further divisions, giving rise to a population of faulty cells that then become tumor tissue.
The researchers made some unexpected discoveries. They found some types of pancreatic cancer have mutations typically seen in colon cancer and leukemia, for which treatments are already available.
Other types bear strong similarities to some bladder and lung cancers, says Prof. Grimmond, “and we can start to draw on that knowledge to improve treatments.”
Using an approach called “integrated genomic analysis,” the team brought together techniques that analyze not only genetic code, but also variations in structure and gene activity. This is the first time such an analysis has revealed so much about the genetic damage that leads to pancreatic cancer.
First author Dr. Peter Bailey, also based both at the University of Melbourne and the University of Glasgow, says the treatments for pancreatic cancer have not changed much in the last 20 years. There are various types of chemotherapy, but it is not very selective, “it’s like hitting the disease with a mallet with your eyes closed,” he notes.
Dr. Bailey says he and his colleagues are trying to change the clinical landscape, not only for pancreatic cancer but for all cancers. We need a better understanding of their molecular origins, he explains, so patients receive a more personalized treatment that targets the specific underlying genetic defects of their individual cancer.
Leanne Reynolds, head of research for Pancreatic Cancer UK, says:
“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 study builds on earlier work by the team as part of the International Cancer Genome Consortium (ICGC). For example, in February 2015, Medical News Today described an earlier study, also published in Nature, that put the case for four distinct types of pancreatic cancer based on the extent of genetic disruption to chromosomes.