Fibroblast activation protein
Fibroblast activation protein (FAP), also called fibroblast activation protein-α, is a cell-surface protein associated particularly with cancer-associated fibroblasts and activated tumor stroma.
Fibroblast activation protein (FAP), also called fibroblast activation protein-α, is a cell-surface protein associated particularly with cancer-associated fibroblasts and activated tumor stroma. Its expression within the tumor microenvironment—and, in some settings, in tumor cells such as those of glioblastoma—has made it a marker of tumor–stroma biology, including spatial niches associated with treatment resistance. FAP-positive stromal cells are therefore being investigated in relation to tumor uptake, collagen-rich tumor architecture, macrophages, and T-lymphocytes.
FAP is a major target for molecular imaging and theranostics. FAP inhibitors labeled with gallium-68, including FAPI-46 and investigational probes such as FXX489, are being evaluated with positron emission tomography and positron emission tomography–computed tomography for tumor characterization, peritoneal disease assessment, and treatment planning. Radioligands labeled with lutetium-177, including 177Lu-DOTA-7ND and dual-targeting 177Lu-DOTA-FAPI-RGD, are being studied for FAP-directed radionuclide therapy, with biodistribution, tumor retention, organ dosimetry, and safety as important considerations. Other approaches combine FAP targeting with Annexin A1, integrin αvβ3, or CD3 to improve tumor localization or recruit T-lymphocytes, positioning FAP as both an imaging biomarker and a potential therapeutic entry point in solid tumors.
- First-in-Human PET/CT Imaging of FXX489, a Second-Generation Cyclic Peptide FAP Inhibitor: A Translational Exploratory Study. PMID 42969700
- 68Ga-NOTA-FAPI-IF7: A Heterobivalent PET Probe for Dual-Targeted Imaging of Fibroblast Activation Protein and Annexin A1 in Tumor Microenvironment. PMID 42969726
Where the papers sit
10 papers from the last 6 months study fibroblast activation protein directly
Study type 1 clinical trial · 1 observational · 1 human data · 6 preclinical · 1 unclassified
Themes 3 themes · 1 new direction
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FAP PET Imaging and Theranostics
Next-generation FAP probes are moving PET imaging toward higher tumor uptake and more adaptable theranostic use. Gallium-68 agents, including FAPI-46 and FXX489, are being evaluated for tumor staging, peritoneal cancer assessment, and glioblastoma characterization. Heterobivalent probes add Annexin A1 or radiotherapeutic motifs to capture tumor microenvironment biology and treatment potential. Albumin binding, hydrophilicity, radiochemical purity, and serum stability remain key determinants of circulation and image quality.
6 papers · 60%
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Tumor-Stroma Immune Targeting
FAP-positive tumor stroma is emerging as both a spatial marker of treatment resistance and a target for immune engagement. Single-cell and spatial multi-omics repeatedly focus attention on the tumor-stroma interface, including tumor-associated macrophages, AXL, and TREM2. The FAP×CD3 bispecific antibody OMTX305 moves this biology toward T-cell-mediated killing in patient-derived solid-tumor models. Whether stromal mapping can select patients or overcome multidrug resistance remains open.
2 papers · 20%
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177Lu FAP Radioligand Therapy
177Lu-labeled FAP ligands are moving from biodistribution and dosimetry studies toward early clinical radioligand therapy. Dual targeting of FAP and integrin αvβ3 with 177Lu-DOTA-FAPI-RGD aims to improve lesion localization, while 177Lu-DOTA-7ND provides a direct FAP-directed therapeutic platform. Safety, organ dosimetry, lymph-node distribution, and stable disease are recurring clinical endpoints. The magnitude and durability of tumor control remain unresolved in these early evaluations.
2 papers · 20%
FAP is presented as a direct glioblastoma-cell target, not only a stromal target
The glioblastoma study using human U-87 MG and murine SB28 models assumed the usual stromal framing in which FAP is a target in the tumor microenvironment, particularly cancer-associated fibroblasts; instead, it reports FAP expression within glioblastoma cells as well as the surrounding microenvironment and evaluates FAPI-46 imaging and radionuclide therapy in both immunocompromised and immunocompetent models. This expands the targetable compartment from FAP-positive stroma to the tumor cells themselves, changing the interpretation of FAP-directed therapy in glioblastoma from stromal targeting alone to potentially combined tumor-cell and stromal targeting 42242868Jun.
Papers
The 10 papers from the last 6 months that study fibroblast activation protein directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
FAP PET Imaging and Theranostics (6)
- 68Ga-NOTA-FAPI-IF7: A Heterobivalent PET Probe for Dual-Targeted Imaging of Fibroblast Activation Protein and Annexin A1 in Tumor Microenvironment. Molecular pharmaceutics · 2 Nov 2026 PMID 42969726
- First-in-Human PET/CT Imaging of FXX489, a Second-Generation Cyclic Peptide FAP Inhibitor: A Translational Exploratory Study. Molecular pharmaceutics · 2 Nov 2026 PMID 42969700
- Heterobivalent fibroblast activation protein-targeted Radiotheranostic ligands integrating cyclic peptide and small-molecule motifs for enhanced tumor retention. Bioorganic chemistry · 11 Sept 2026 PMID 42727450
- [18F]AlF-FAPI-74 PET/CT for preoperative assessment of the peritoneal cancer index and comparison with MRI-based, surgical and pathological assessment in colorectal cancer patients eligible for CRS-HIPEC: study protocol for a prospective observational proof-of-concept study. BMJ open · 9 Sept 2026 PMID 42716685
- Translational Theranostics in Glioblastoma: FAPI-46 as a Precision Medicine Tool. Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 4 Jun 2026 PMID 42242868
- Structural stability of human serum albumin complexes governs the blood circulation of gallium-Labeled FAP inhibitors. Bioorganic chemistry · 22 May 2026 PMID 42172798
Tumor-Stroma Immune Targeting (2)
- Single-cell and spatial multi-omics reveal a recurrent multicellular niche at the tumor-stroma interface in multidrug resistance. Cell reports. Medicine · 16 Sept 2026 PMID 42748914
- The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors. Science advances · 11 Sept 2026 PMID 42726846
177Lu FAP Radioligand Therapy (2)
- Safety, Biodistribution, and Dosimetry of FAP and Integrin αvβ3 Dual-Targeting Radioligand 177Lu-DOTA-FAPI-RGD: Preclinical Validation and First-in-Human Study in Patients with Advanced Adenocarcinomas. Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 20 Aug 2026 PMID 42624650
- Preclinical and first-in-human pilot evaluation of 177Lu-DOTA-7ND for fibroblast activation protein-α-targeted radionuclide imaging and therapy. Journal of controlled release : official journal of the Controlled Release Society · 20 Aug 2026 PMID 42624433
By study type
Clinical trials (1)
- Safety, Biodistribution, and Dosimetry of FAP and Integrin αvβ3 Dual-Targeting Radioligand 177Lu-DOTA-FAPI-RGD: Preclinical Validation and First-in-Human Study in Patients with Advanced Adenocarcinomas. Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 20 Aug 2026 PMID 42624650
Observational studies and case reports (1)
- [18F]AlF-FAPI-74 PET/CT for preoperative assessment of the peritoneal cancer index and comparison with MRI-based, surgical and pathological assessment in colorectal cancer patients eligible for CRS-HIPEC: study protocol for a prospective observational proof-of-concept study. BMJ open · 9 Sept 2026 PMID 42716685
Human data, design not indexed (1)
- Structural stability of human serum albumin complexes governs the blood circulation of gallium-Labeled FAP inhibitors. Bioorganic chemistry · 22 May 2026 PMID 42172798
Preclinical: animal, cell and lab studies (6)
- 68Ga-NOTA-FAPI-IF7: A Heterobivalent PET Probe for Dual-Targeted Imaging of Fibroblast Activation Protein and Annexin A1 in Tumor Microenvironment. Molecular pharmaceutics · 2 Nov 2026 PMID 42969726
- First-in-Human PET/CT Imaging of FXX489, a Second-Generation Cyclic Peptide FAP Inhibitor: A Translational Exploratory Study. Molecular pharmaceutics · 2 Nov 2026 PMID 42969700
- Heterobivalent fibroblast activation protein-targeted Radiotheranostic ligands integrating cyclic peptide and small-molecule motifs for enhanced tumor retention. Bioorganic chemistry · 11 Sept 2026 PMID 42727450
- The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors. Science advances · 11 Sept 2026 PMID 42726846
- Preclinical and first-in-human pilot evaluation of 177Lu-DOTA-7ND for fibroblast activation protein-α-targeted radionuclide imaging and therapy. Journal of controlled release : official journal of the Controlled Release Society · 20 Aug 2026 PMID 42624433
- Translational Theranostics in Glioblastoma: FAPI-46 as a Precision Medicine Tool. Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 4 Jun 2026 PMID 42242868
Unclassified: not yet indexed with MeSH (1)
- Single-cell and spatial multi-omics reveal a recurrent multicellular niche at the tumor-stroma interface in multidrug resistance. Cell reports. Medicine · 16 Sept 2026 PMID 42748914
Written from 10 PubMed abstracts, each one listed by PMID above. Published: 2026-11-04. Drafted by language models from published abstracts; not medical advice.