Unraveling the roles of fibroblast activation protein-positive cancer-associated fibroblasts in cancer: From mechanisms to therapy (Review)

Sep 23, 2026

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) actively shape tumor pathogenesis, with fibroblast activation protein (FAP)+ CAFs representing the dominant CAF subtype across multiple cancers, including breast, lung, and pancreatic malignancies. Their contribution to tumor progression is central but incomplete biological understanding limits clinical translation. This review consolidates key characteristics, functions, and mechanisms of FAP+ CAFs in tumor growth, extracellular matrix organization, tumor expansion, and immunomodulation, and discusses FAP+ CAF-based diagnostic and therapeutic strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

1. Introduction

2. FAP+ CAFs

3. FAP+ CAF function in cancer progression

4. Association between FAP+ CAFs and clinicopathological variables

5. FAP+ CAF targeting applications in diagnosis and therapeutics

6. Conclusion

INTERNATIONAL JOURNAL OF ONCOLOGY 69: 90, 2026 Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review) ZHIXIN TAO, ZHUAN ZHOU, YONG WU and JINWEI HU Department of Laboratory Medicine, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), Changsha, Hunan 410005, P.R. China Received February 11, 2026; Accepted June 2, 2026 DOI: 10.3892/ijo.2026.5903 Abstract. Cancer‑associated fibroblasts (CAFs) in the tumor microenvironment (TME) are involved in tumor pathogenesis. Fibroblast activation protein (FAP)+ CAFs are the predominant CAF subtype across multiple cancer types, including breast, lung and pancreatic cancer. FAP+ CAFs are crucial contribu‑ tors to tumor progression. However, incomplete understanding of the biology of FAP+ CAFs limits their potential for clinical application . The present review aimed to summarize the characteristic features, functions and underlying mechanisms of FAP+ CAFs in tumor growth, including their involvement in extracellular matrix organization, tumor expansion and immunomodulation within the TME, in which FAP plays an important role, and FAP+ CAF‑based strategies for tumor diag‑ nosis and therapeutic intervention. The present study aimed to provide a conceptual framework for the multifaceted roles of FAP+ CAFs in cancer progression to guide development of optimized FAP+ CAF‑targeted diagnostics and therapies. Contents 1. Introduction 2. FAP+ CAFs 3. FAP+ CAF function in cancer progression Correspondence to: Dr Jinwei Hu, Department of Laboratory Medicine, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), 311 Yingpan Road, Changsha, Hunan 410005, P.R. China E‑mail: [cshujinwei@163.com](cshujinwei@163.com) Abbreviations: FAP, fibroblast activation protein; ECM, extracellular matrix; TME, tumor microenvironment; ap, antigen‑presenting; iCAF, inflammatory cancer‑associated fibroblast; my, myofibroblastic Key words: cancer‑associated fibroblast, fibroblast activation protein, tumor progression, tumor microenvironment, cancer therapy 4. Association between FAP+ CAFs and clinicopathological variables 5. FAP+ CAF targeting applications in diagnosis and therapeutics 6. Conclusion 1. Introduction Since the ‘seed and soil’ theory was proposed in 1889 to describe the association between tumor cells and their surrounding environment (1), a growing number of researchers have recog‑ nized the importance of the tumor microenvironment (TME) in tumor development (2‑4). As the ‘soil’ for tumor cell growth, the TME contains nutrients, regulatory factors, extracellular matrix (ECM), intertwined blood vessels and diverse stromaland immune cells (5) . Interactions between the components within the TME drive dynamic changes and the alterations of properties or quantities in certain components, such as decreased T cell function, increased stromal density and rising levels of inflammatory cytokines, may affect tumor growth (3) . Cancer‑associated fibroblasts (CAFs) are prominent stromal cells within the TME and influence tumor behavior through multiple complex mechanisms (4) . Furthermore, they impede the efficacy of various tumor therapies, including radiotherapy, chemotherapy and immunotherapy by enhancing tumor cell stemness and eliciting immunosuppression (5,6) . CAF characterization primarily relies on morphology (elongated or stellate shape), biological properties and expres‑ sion of canonical biomarkers including α smooth muscle actin (α‑SMA), vimentin, fibroblast activation protein (FAP), platelet‑derived growth factor receptors (PDGFRs), podoplanin, periostin (POSTN), transgelin (TAGLN), collagen (COL)1A1, COL1A2 and S100A4 (7) . However, that these markers are not universally co‑expressed across all CAFs (6) . For example, in glioblastoma, the majority

FAQs

What is the role of FAP+ cancer-associated fibroblasts in the tumor microenvironment?

FAP+ CAFs are a predominant CAF subtype in many cancers and contribute crucially to tumor progression within the TME through effects on tumor growth, extracellular matrix organization, tumor expansion, and immunomodulation.

Why is better understanding of FAP+ CAF biology important for clinical use?

The review highlights that incomplete understanding of FAP+ CAF biology limits their potential for clinical application, including optimized diagnostics and therapies.

How can FAP+ CAFs be characterized and studied experimentally?

CAF characterization relies on morphology, canonical biomarker expression (including FAP and other markers), and FAP+ CAFs can be efficiently isolated by fluorescence-activated cell sorting due to FAP cell-surface localization for mechanistic investigation.

Sep 23, 2026

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