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Pancreatic tumours in mice, like those in people, have so few blood vessels that chemotherapy barely reaches them; stripping away the surrounding scar tissue with a hedgehog-blocking drug let more gemcitabine in and held the disease still for a while.
A mouse model of pancreatic ductal adenocarcinoma refractory to gemcitabine was studied; tumours were poorly perfused and poorly vascularised, properties shared with human disease. Co-administration of IPI-926, which depletes tumour-associated stroma by inhibiting hedgehog signalling, produced a transient increase in intratumoural vascular density and gemcitabine concentration, leading to transient stabilisation of disease. Inefficient drug delivery may therefore be an important contributor to chemoresistance.
It launched a decade of attempts to strip the stroma to let drugs in; the clinical trials that followed failed, and later mouse work showed the stroma also restrains the tumour.
Shares Hedgehog signalling, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares David A. Tuveson, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares David A. Tuveson, Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares David A. Tuveson, Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.