Targeting cancer-associated fibroblasts: Challenges, opportunities and future directions
Targeting cancer-associated fibroblasts: Challenges, opportunities and future directions
Cancer-associated fibroblasts (CAFs) are a common cell in the tumour microenvironment with diverse tumour-promoting functions. Their presence in tumours is commonly associated with poor prognosis making them attractive therapeutic targets, particularly in the context of immunotherapy where CAFs have been shown to promote resistance to checkpoint blockade. Previous attempts to inhibit CAFs clinically have not been successful, however, in part due to a lack of understanding of CAF heterogeneity and function, with some fibroblast populations potentially being tumour suppressive. Recent single-cell transcriptomic studies have advanced our understanding of fibroblast phenotypes in normal tissues and cancers, allowing for a more precise characterisation of CAF subsets and providing opportunities to develop new therapies. Here we review recent advances in the field, focusing on the evolving area of therapeutic CAF targeting.
Cancer -associated fibroblast, Fibroblast, Immunotherapy, Myofibroblast, Stromal targeting, Tumour microenvironment
Jenkins, Benjamin H.
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Buckingham, Josephine F.
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Hanley, Christopher J.
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Thomas, Gareth J.
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1 December 2022
Jenkins, Benjamin H.
d4bff137-9406-401c-9b30-8df72de88176
Buckingham, Josephine F.
e0e5f0b1-ff44-48da-adb4-cadac56a6e06
Hanley, Christopher J.
44c46dcb-d239-4d41-9fc5-ca7c2efad6cc
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Jenkins, Benjamin H., Buckingham, Josephine F., Hanley, Christopher J. and Thomas, Gareth J.
(2022)
Targeting cancer-associated fibroblasts: Challenges, opportunities and future directions.
Pharmacology and Therapeutics, 240, [108231].
(doi:10.1016/j.pharmthera.2022.108231).
Abstract
Cancer-associated fibroblasts (CAFs) are a common cell in the tumour microenvironment with diverse tumour-promoting functions. Their presence in tumours is commonly associated with poor prognosis making them attractive therapeutic targets, particularly in the context of immunotherapy where CAFs have been shown to promote resistance to checkpoint blockade. Previous attempts to inhibit CAFs clinically have not been successful, however, in part due to a lack of understanding of CAF heterogeneity and function, with some fibroblast populations potentially being tumour suppressive. Recent single-cell transcriptomic studies have advanced our understanding of fibroblast phenotypes in normal tissues and cancers, allowing for a more precise characterisation of CAF subsets and providing opportunities to develop new therapies. Here we review recent advances in the field, focusing on the evolving area of therapeutic CAF targeting.
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Jenkins, Buckingham et al
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e-pub ahead of print date: 17 June 2022
Published date: 1 December 2022
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Keywords:
Cancer -associated fibroblast, Fibroblast, Immunotherapy, Myofibroblast, Stromal targeting, Tumour microenvironment
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Local EPrints ID: 470300
URI: http://eprints.soton.ac.uk/id/eprint/470300
ISSN: 0163-7258
PURE UUID: 1755480a-3847-4295-8815-ba6882f9879e
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Date deposited: 05 Oct 2022 16:59
Last modified: 18 Mar 2024 05:29
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Author:
Benjamin H. Jenkins
Author:
Josephine F. Buckingham
Author:
Christopher J. Hanley
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