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      Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects

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          Abstract

          Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.

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          A framework for advancing our understanding of cancer-associated fibroblasts

          Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
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            FSP1 is a glutathione-independent ferroptosis suppressor

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              Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

              Öhlund et al. develop a three-dimensional co-culture platform of neoplastic pancreatic ductal organoids and pancreatic stellate cells (PSCs) to characterize the dynamic crosstalk between cancer cells and stromal cells, and to address stromal heterogeneity. The co-cultures reveal the co-existence of two phenotypically distinct populations of PSCs, providing insights into PDA biology and prompting a reconsideration of interventional strategies.
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                Author and article information

                Contributors
                Zhipeng.Cao@onjcri.org.au
                Andrew.Scott@onjcri.org.au
                Journal
                J Biomed Sci
                J Biomed Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                9 January 2025
                9 January 2025
                2025
                : 32
                : 7
                Affiliations
                [1 ]Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, ( https://ror.org/04t908e09) Melbourne, VIC 3084 Australia
                [2 ]School of Cancer Medicine, La Trobe University, ( https://ror.org/01rxfrp27) Melbourne, VIC 3086 Australia
                [3 ]Department of Molecular Imaging and Therapy, Austin Health, ( https://ror.org/05dbj6g52) Melbourne, VIC 3084 Australia
                [4 ]Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, ( https://ror.org/02bfwt286) Melbourne, VIC 3800 Australia
                [5 ]Department of Medicine, University of Melbourne, ( https://ror.org/01ej9dk98) Melbourne, VIC 3010 Australia
                Author information
                http://orcid.org/0000-0003-4142-6190
                Article
                1099
                10.1186/s12929-024-01099-2
                11715488
                39780187
                b1cdce81-43a3-4b6c-972c-e8b6246cf00b
                © The Author(s) 2025

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 5 April 2024
                : 9 November 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1177837
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100015572, National Imaging Facility;
                Categories
                Review
                Custom metadata
                © National Science Council of the Republic of China (Taiwan) 2025

                Molecular medicine
                tumour microenvironment,cancer-associated fibroblasts,tumour stroma,targeted therapy,clinical trials

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