Article summary written by Kate O’Rourke
“Genomic analyses identify molecular subtypes of pancreatic cancer” published in Nature
A genomic analysis by a multinational group of researchers has led to a reclassification of pancreatic cancer into four distinct subtypes, each with a different cause and each requiring a different treatment approach. The study, reported in Nature (2016;531(7592):47-52), will help in the quest to develop personalized treatments for pancreatic cancer.
Since the 1990s, a number of targeted therapies have been developed for cancers including breast, lung, and melanoma, but unfortunately, those treating pancreatic cancer have had to contend with non-targeted drugs. Pancreatic cancer has a median survival measured in months and a five-year survival of less than 5%.
The new study was spearheaded by the Australian Pancreatic Genome Initiative, an international program of research that has been working since 2013 to improve outcomes for patients with pancreatic cancer. In the study, led by Andrew Biankin, MD, formerly of the Garvan Institute of Medical Research and now Regius Chair of Surgery/Director of Translational Research Centre, Wolfson Wohl Cancer Research Centre, University of Glasgow, investigators performed genomic analyses on 456 pancreatic ductal adenocarcinomas, assessing expression of genes, mutational profiles, and epigenetic changes. They identified four distinct subtypes: squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX).
The four subtypes have distinct clinical characteristics and different prognoses. Squamous pancreatic tumors are associated with a poor prognosis and are enriched for mutations in genes including TP53 and KDM6A. This subtype resembles other squamous tumors that occur in the breast, bladder, lung, and head and neck cancer. The pancreatic progenitor subtype preferentially expresses genes involved in early pancreatic development (FOXA2/3, PDX1, and MNX1). ADEX tumors are associated with upregulation of genes that regulate networks involved in KRAS activation, as well as exocrine and endocrine differentiation. The immunogenic subtype shares many of the characteristics of the pancreatic progenitor class, but is associated with upregulated immune networks.
The identification of the four subtypes is a huge step forward in understanding the molecular pathology of pancreatic cancer. Researchers believe the new knowledge will improve patient selection and help researchers identify targeted drugs for pancreatic cancer. The researchers are especially hopeful that they will be able to identify drugs targeting the immunogenic subtype, which may be responsive to some of the immunotherapies on the market or in development for other solid tumor cancers.
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