{"entity":{"id":"paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009","kind":"paper","name":"Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Olive et al., Science 2009: hedgehog inhibition improves gemcitabine delivery in the mouse model","url":"https://doi.org/10.1126/science.1171362"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19460966/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":["hedgehog","caf-activation-desmoplasia"],"terms":["desmoplasia"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2009,"doi":"10.1126/science.1171362","pmid":"19460966","authors":"Olive KP, Jacobetz MA, Davidson CJ, et al.","paperType":"basic","findings":["Mouse and human pancreatic tumours are poorly perfused and vascularised.","Hedgehog inhibition transiently raised vascular density and intratumoural gemcitabine and stabilised disease."],"whatItMeans":"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.","caveats":["Mouse model, transient effect.","Hedgehog inhibitors were harmful or futile in patients (Rhim 2014, Ozdemir 2014)."],"changedPractice":false},"route":"/key-papers/paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"hedgehog","kind":"pathway","name":"Hedgehog signalling","route":"/pathways/hedgehog/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"}],"person":[{"id":"david-tuveson","kind":"person","name":"David A. Tuveson","route":"/people/david-tuveson/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}