Exploring the biology of cancer-associated fibroblasts in pancreatic cancer

Bryce, A. S. , Dreyer, S. B., Froeling, F. E.M. and Chang, D. K. (2022) Exploring the biology of cancer-associated fibroblasts in pancreatic cancer. Cancers, 14(21), 5302. (doi: 10.3390/cancers14215302) (PMID:36358721) (PMCID:PMC9659154)

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterised by a stubbornly low 5-year survival which is essentially unchanged in the past 5 decades. Despite recent advances in chemotherapy and surgical outcomes, progress continues to lag behind that of other cancers. The PDAC microenvironment is characterised by a dense, fibrotic stroma of which cancer-associated fibroblasts (CAFs) are key players. CAFs and fibrosis were initially thought to be uniformly tumour-promoting, however this doctrine is now being challenged by a wealth of evidence demonstrating CAF phenotypic and functional heterogeneity. Recent technological advances have allowed for the molecular profiling of the PDAC tumour microenvironment at exceptional detail, and these technologies are being leveraged at pace to improve our understanding of this previously elusive cell population. In this review we discuss CAF heterogeneity and recent developments in CAF biology. We explore the complex relationship between CAFs and other cell types within the PDAC microenvironment. We discuss the potential for therapeutic targeting of CAFs, and we finally provide an overview of future directions for the field and the possibility of improving outcomes for patients with this devastating disease.

Item Type:Articles
Additional Information:No external funding was obtained for this review. D.K.C. receives funding from Cancer Research UK for the Precision-Panc platform (C51058/A25407) and from the Cancer Research UK Scotland Centre (CTRQQR-2021\100006). S.B.D. holds a Chief Scientist Office Postdoctoral Clinical Lectureship (PCL/22/03). F.E.M.F. holds a McNab fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chang, Professor David and Dreyer, Dr Stephan and Bryce, Mr Adam and Froeling, Dr Fieke
Authors: Bryce, A. S., Dreyer, S. B., Froeling, F. E.M., and Chang, D. K.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Cancers
Publisher:MDPI
ISSN:2072-6694
ISSN (Online):2072-6694
Published Online:28 October 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Cancers 14(21): 5302
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174159Precision-Panc: a dynamic therapeutic development platform for pancreatic cancerDavid ChangCancer Research UK (CRUK)C51058/A25407CS -Translational Research Centre