{"entity":{"id":"paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014","kind":"paper","name":"Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma","aka":[],"tldr":"Removing the hedgehog signal that builds the scar tissue around pancreatic tumours in mice gave less stroma but more aggressive, more vascular cancers, and only anti-angiogenic treatment helped them.","summary":"Sonic hedgehog, overexpressed by neoplastic cells and driving a fibroblast-rich desmoplastic stroma, was deleted in a mouse model of pancreatic ductal adenocarcinoma. Shh-deficient tumours had reduced stromal content but were more aggressive, undifferentiated, more vascular and more proliferative, effects fully recapitulated by a smoothened inhibitor in control mice. VEGFR blockade selectively improved survival of Shh-deficient tumours, indicating that hedgehog-driven stroma suppresses tumour growth partly by restraining angiogenesis.","asOf":"2026-09-24","links":[{"label":"Rhim et al., Cancer Cell 2014: stromal elements restrain pancreatic cancer","url":"https://doi.org/10.1016/j.ccr.2014.04.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24856585/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["columbia-hicc"],"pathways":["hedgehog","caf-activation-desmoplasia","vegf-angiogenesis"],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccr.2014.04.021","pmid":"24856585","authors":"Rhim AD, Oberstein PE, Thomas DH, et al.","paperType":"basic","findings":["Hedgehog deletion or smoothened inhibition reduced stroma but produced more aggressive, vascular tumours.","VEGFR blockade selectively helped stroma-depleted tumours."],"whatItMeans":"Published alongside Ozdemir, it explains why the hedgehog inhibitor trials in patients failed and why stromal targets are now chosen for their signalling rather than their bulk.","caveats":["Mouse genetics and models.","Does not exclude benefit from selective stromal reprogramming."],"changedPractice":false},"route":"/key-papers/paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"institution":[{"id":"columbia-hicc","kind":"institution","name":"Herbert Irving Comprehensive Cancer Center, Columbia University","route":"/institutions/columbia-hicc/"}],"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/"},{"id":"vegf-angiogenesis","kind":"pathway","name":"VEGF angiogenesis","route":"/pathways/vegf-angiogenesis/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"}],"journal":[{"id":"cancer-cell","kind":"journal","name":"Cancer Cell","route":"/journals/cancer-cell/"}]}}