On the origin of pancreatic cancer: Molecular Tumor Subtypes in Perspective of Exocrine Cell Plasticity

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating type of cancer. While many studies have shed light into the pathobiology of PDAC, the nature of PDAC's cell of origin remains under debate. Studies in adult pancreatic tissue have unveiled a remarkable exocrine cell plasticity including transitional states, mostly exemplified by acinar to ductal cell metaplasia, but also with recent evidence hinting at duct to basal cell transitions. Single cell RNA sequencing has further revealed intrapopulation heterogeneity among acinar and duct cells. Transcriptomic and epigenomic relationships between these exocrine cell differentiation states and PDAC molecular subtypes have started to emerge, suggesting different ontogenies for different tumor subtypes. This review sheds light on these diverse aspects with particular focus on studies with human cells. Understanding the 'masked ball' of exocrine cells at origin of PDAC and leaving behind the binary acinar versus duct cell classification may significantly advance our insights in PDAC biology.

Originele taal-2English
Pagina's (van-tot)1243-1253
Aantal pagina's11
TijdschriftCellular and molecular gastroenterology and hepatology
Volume13
Nummer van het tijdschrift4
DOI's
StatusPublished - 4 dec 2021

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Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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