S Martens1, P Lefesvre2, R Nicolle3, A V Biankin4, F Puleo5, J L Van Laethem6, I Rooman7. 1. Laboratory of Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels. 2. Department of Pathology, UZ Brussel, Brussels, Belgium. 3. Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France. 4. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. 5. Medical Oncology Department, Institut Jules Bordet; Laboratory of Experimental Gastroenterology. 6. Laboratory of Experimental Gastroenterology; Department of Gastroenterology and Digestive Oncology, Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: jl.vanlaethem@erasme.ulb.ac.be. 7. Laboratory of Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels. Electronic address: irooman@vub.be.
Abstract
BACKGROUND: Different histological and molecular subtypes of pancreatic ductal adenocarcinoma (PDAC), with different molecular composition and survival statistics, have recently been recognised. MATERIALS AND METHODS: This review describes the currently available studies regarding molecular and histological subtypes in PDAC. Studies from major cohorts such as International Cancer Genome Consortium as well as smaller cohorts are reviewed. We discuss where the described subtypes overlap, where the discrepancies are and which paths forward could be taken regarding diagnosis, ontogeny and therapy. RESULTS: Four molecular subtypes with strong overlap among the different studies can be found, next to a list of mixed findings. Two of the four subtypes (epithelial classical and mesenchymal basal-like) were represented in every study and were often discriminated in other solid tumours as well. These two subtypes differ substantially in prognosis. One biomarker has been discovered, only discriminating these two subtypes, and insights into subtype-specific therapeutic vulnerabilities are scarce. CONCLUSION: Subtypes can be reproducibly detected in cohorts of PDAC patients and two of them directly relate with prognosis. A consensus on the subtypes is warranted. Further discovery and validation studies are needed to identify strong biomarkers, to comprehend subtype ontogeny and to define strategies for precision medicine.
BACKGROUND: Different histological and molecular subtypes of pancreatic ductal adenocarcinoma (PDAC), with different molecular composition and survival statistics, have recently been recognised. MATERIALS AND METHODS: This review describes the currently available studies regarding molecular and histological subtypes in PDAC. Studies from major cohorts such as International Cancer Genome Consortium as well as smaller cohorts are reviewed. We discuss where the described subtypes overlap, where the discrepancies are and which paths forward could be taken regarding diagnosis, ontogeny and therapy. RESULTS: Four molecular subtypes with strong overlap among the different studies can be found, next to a list of mixed findings. Two of the four subtypes (epithelial classical and mesenchymal basal-like) were represented in every study and were often discriminated in other solid tumours as well. These two subtypes differ substantially in prognosis. One biomarker has been discovered, only discriminating these two subtypes, and insights into subtype-specific therapeutic vulnerabilities are scarce. CONCLUSION: Subtypes can be reproducibly detected in cohorts of PDAC patients and two of them directly relate with prognosis. A consensus on the subtypes is warranted. Further discovery and validation studies are needed to identify strong biomarkers, to comprehend subtype ontogeny and to define strategies for precision medicine.
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