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The scaffolding cells that tumours recruit to build scar-like tissue around themselves. They feed the cancer, block drugs and immune cells, and carry the FAP protein that PET scans can now see.
Heterogeneous (myCAF, iCAF, apCAF); sources include resident fibroblasts, stellate cells, and mesenchymal stem cells. Secrete TGF-β, IL-6, CXCL12; deposit ECM. Depletion experiments show both pro- and anti-tumour roles, so targeting is moving toward reprogramming (vitamin D receptor agonists) and FAP-directed theranostics.
In plain words · FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
Showing the target this term concerns: FAP.
The classical versus basal-like split, later tied to GATA6 expression and to chemotherapy response, is the subtype scheme most likely to reach the clinic; the stromal subtypes are why the desmoplastic stroma is treated as a partner in the disease rather than inert scar.
Together with the negative HALO-301 trial of hyaluronidase this ended the first, blunt version of stromal targeting; second-generation ideas aim to reprogramme rather than remove the stroma.
This review is the standard map of the tumour microenvironment and the reason microenvironment-directed drugs, from anti-angiogenics to macrophage and fibroblast targeting agents, are developed alongside tumour-cell-directed ones.
Shares Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Mechanical theory: stiffness, pressure and force as causes, Desmoplasia (tumour stroma).
Shares Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma, Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Desmoplasia (tumour stroma).
Shares Invasion: proteases, adhesion & the invasive front, Desmoplasia (tumour stroma), FAP, Fibroblast activation, desmoplasia & matrix stiffness.
Shares Desmoplasia (tumour stroma), FAP, Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME).
Shares Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, FAPI PET, FAP, Radioligand therapy (beta emitters).
Shares Tissue organisation field theory (Sonnenschein and Soto), Mechanical theory: stiffness, pressure and force as causes.
Shares FAPI PET, FAP, Fibroblast activation, desmoplasia & matrix stiffness.
Shares FAPI PET, FAP, TGF-β signalling, Tumour microenvironment (TME).