Oncology Central

Genomic analysis defines four pancreatic cancer subtypes

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Details of a reclassification of pancreatic cancer into four distinct subtypes were recently published in Nature. These four subtypes of the disease were demonstrated to be associated with their own clinical characteristics and survival outcomes.

Following genomic analysis of data sets from the Australian Pancreatic Cancer Genome Initiative – which included investigation of tumor mutational profile, gene expression and epigenetic changes of 456 pancreatic ductal adenocarcinomas – the disease was categorized as squamous, pancreatic progenitor, immunogenic or aberrantly differentiated endocrine exocrine (ADEX).

The researchers behind the study hope that this new classification will aid in the selection of appropriate targeted therapy for each subtype of pancreatic cancer. This would be an improvement on current methods of treating pancreatic cancer, which are not targeted or selective and have been described as “hitting the disease with a mallet with your eyes closed”.

As study co-lead Andrew Biankin of the University of Glasgow (UK) explained: “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 personalized therapeutic options for individual patients and a launch pad to investigate new treatments.”

Key characteristics of each of the subtypes described in the study include:

  • Squamous: a high proportion of the genes associated with this subtype of pancreatic cancer also demonstrate notable expression in squamous-like tumors of the breast, bladder, lung, and head and neck
  • Pancreatic progenitor: characterized by the preferential expression of genetic networks that regulate early embryonic development of the pancreas
  • ADEX: defined by transcriptional networks that are important in later stages of pancreatic development and differentiation, and is a subclass of pancreatic progenitor tumors
  • Immunogenic: similar to the pancreatic progenitor subgroup but also noted for significant immune infiltrate and activation of acquired immune suppression

One of the key findings of this study is the definition of an immunogenic subtype of pancreatic cancer, which could be responsive to cancer immunotherapy.

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

“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 personalized or precise approach to treatment based on the underlying genetic defects that drive a cancer that may be vulnerable to specific drugs,” explained first author Peter Bailey the University of Glasgow.

Sources: Bailey P, Chang DK, Nones K et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. doi: 10.1038/nature16965 (2016) [Epub ahead of print]; University of Glasgow press release

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