Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities

Fibroblast Activation Protein (FAP) has emerged as a critical player in cancer biology, particularly in shaping the tumour microenvironment (TME) and influencing immunotherapy outcomes. FAP-positive cancer-associated fibroblasts (CAFs) play multiple roles in tumour progression and immune modulation....

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Main Authors: Hsing Hwa Lee, Zeyad Al-Ogaili
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Oncology Reviews
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/or.2025.1617487/full
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author Hsing Hwa Lee
Zeyad Al-Ogaili
author_facet Hsing Hwa Lee
Zeyad Al-Ogaili
author_sort Hsing Hwa Lee
collection DOAJ
description Fibroblast Activation Protein (FAP) has emerged as a critical player in cancer biology, particularly in shaping the tumour microenvironment (TME) and influencing immunotherapy outcomes. FAP-positive cancer-associated fibroblasts (CAFs) play multiple roles in tumour progression and immune modulation. FAP, predominantly expressed on CAFs, contributes significantly to extracellular matrix remodelling, angiogenesis, and the creation of an immunosuppressive milieu. There are complex interactions between FAP-positive CAFs and various components of the immune system, highlighting their impact on T cell function and macrophage polarisation. This makes FAP a promising target for cancer therapy and potentially as a biomarker for immunotherapy treatment response. This review highlights the clinical challenges to target FAP and also addresses the heterogeneity of CAFs with the need for more refined characterisation to enhance therapeutic strategies and future research directions.
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publisher Frontiers Media S.A.
record_format Article
series Oncology Reviews
spelling doaj-art-b6e3a2c1cc254a87bc662ac1b46fbade2025-08-20T02:40:30ZengFrontiers Media S.A.Oncology Reviews1970-55572025-07-011910.3389/or.2025.16174871617487Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunitiesHsing Hwa Lee0Zeyad Al-Ogaili1Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, AustraliaDepartment of Nucelar Medicine, Fiona StanleyHospital, Perth, WA, AustraliaFibroblast Activation Protein (FAP) has emerged as a critical player in cancer biology, particularly in shaping the tumour microenvironment (TME) and influencing immunotherapy outcomes. FAP-positive cancer-associated fibroblasts (CAFs) play multiple roles in tumour progression and immune modulation. FAP, predominantly expressed on CAFs, contributes significantly to extracellular matrix remodelling, angiogenesis, and the creation of an immunosuppressive milieu. There are complex interactions between FAP-positive CAFs and various components of the immune system, highlighting their impact on T cell function and macrophage polarisation. This makes FAP a promising target for cancer therapy and potentially as a biomarker for immunotherapy treatment response. This review highlights the clinical challenges to target FAP and also addresses the heterogeneity of CAFs with the need for more refined characterisation to enhance therapeutic strategies and future research directions.https://www.frontiersin.org/articles/10.3389/or.2025.1617487/fullfibroblast activation protein (FAP)cancer associate fibroblasts (CAFs)tumour microenvironment (TME)immunotherapycancer
spellingShingle Hsing Hwa Lee
Zeyad Al-Ogaili
Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
Oncology Reviews
fibroblast activation protein (FAP)
cancer associate fibroblasts (CAFs)
tumour microenvironment (TME)
immunotherapy
cancer
title Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
title_full Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
title_fullStr Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
title_full_unstemmed Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
title_short Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities
title_sort fibroblast activation protein and the tumour microenvironment challenges and therapeutic opportunities
topic fibroblast activation protein (FAP)
cancer associate fibroblasts (CAFs)
tumour microenvironment (TME)
immunotherapy
cancer
url https://www.frontiersin.org/articles/10.3389/or.2025.1617487/full
work_keys_str_mv AT hsinghwalee fibroblastactivationproteinandthetumourmicroenvironmentchallengesandtherapeuticopportunities
AT zeyadalogaili fibroblastactivationproteinandthetumourmicroenvironmentchallengesandtherapeuticopportunities