Loading
The dense scar-like tissue that makes up most of a pancreatic tumour, walling off cancer cells from drugs and immune cells.
Cancer-associated fibroblasts, collagen, and hyaluronan can constitute 70-90% of PDAC volume, compressing vessels, limiting drug delivery, and excluding T cells. Stroma-depleting strategies failed or harmed (hedgehog inhibitors, PEGPH20 in HALO-301), revealing that stroma also restrains tumours. FAP-expressing fibroblasts are now an imaging and radioligand target rather than a depletion target.
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.
It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.
The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.
The reference for why pancreatic microenvironment trials read as a list of failures and what the field now means by remodelling rather than removing the stroma.
The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.
It means a CMS4 call on a bulk sample partly measures how much stroma was in the block, which is both a caution for the classification and a pointer to the stroma as the thing to treat.
It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations in trials.
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.
Shares Stromal contribution to the colorectal cancer transcriptome, Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer, The tumour microenvironment in pancreatic cancer: clinical challenges and opportunities, Spatially confined sub-tumor microenvironments in pancreatic cancer.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), FAP, TGF-β signalling, Cold tumours: immune deserts and exclusion.
Shares Stromal contribution to the colorectal cancer transcriptome, Soften the tissue that new metastases need in order to grow, Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6.
Shares Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, FAPI PET, FAP, Cold tumours and the immunosuppressive microenvironment.
Shares Invasion: proteases, adhesion & the invasive front, FAPI PET, FAP, Fibroblast activation, desmoplasia & matrix stiffness.
Shares Soften the tissue that new metastases need in order to grow, Match therapy to the type of scar-forming cell in the tumour, FAP.
Shares Cancer-associated fibroblasts (CAFs), Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma, Invasion: proteases, adhesion & the invasive front, FAP.
Shares Pegvorhyaluronidase alfa, HALO 109-301, Pancreatic ductal adenocarcinoma.