Heterogeneity in the pancreatic cancer microenvironment – TGFβ as a master regulator?

Morton, J. P. and Watt, D. M. (2021) Heterogeneity in the pancreatic cancer microenvironment – TGFβ as a master regulator? Cancers, 13(19), 4984. (doi: 10.3390/cancers13194984) (PMID:34638468) (PMCID:PMC8508541)

Abstract

Pancreatic ductal adenocarcinoma is an aggressive disease for which there are very few available therapies. It is notable for its high degree of tumour complexity, with the tumour microenvironment often accounting for the majority of the tumour volume. Until recently, the biology of the stroma was poorly understood, particularly in terms of heterogeneity. Recent research, however, has shed light on the intricacy of signalling within the stroma and particularly the molecular and functional heterogeneity of the cancer associated fibroblasts. In this review, we summarise the recent improvements in our understanding of the different fibroblast populations within PDAC, with a focus on the role TGFβ plays to dictate their formation and function. These studies have highlighted some of the reasons for the failure of trials targeting the tumour stroma, however, there are still considerable gaps in our knowledge, and more work is needed to make effective fibroblast targeting a reality in the clinic.

• Item Type: Articles
• Additional Information: Funding: This work was supported by Cancer Research UK (JPM: A17196, A29996, A23526, A31287, DW: A17196, A31287).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Morton, Professor Jen
• Authors: Morton, J. P., and Watt, D. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• Published Online: 04 October 2021
• Copyright Holders: Copyright: © 2021 by the authors
• First Published: First published in Cancer 13(19): 4984
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
174160		Precision Panc	Andrew Biankin	Cancer Research UK (CRUK)	C29717/A23526	CS -Translational Research Centre