{"entity":{"id":"idea-reg-losartan-pancreatic-stroma","kind":"idea","name":"Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3","aka":[],"tldr":"A cheap blood pressure drug may soften the dense scar tissue around pancreatic tumours so chemotherapy and immune cells can get in. Early trials look encouraging.","summary":"Losartan inhibits angiotensin II and TGF-beta-driven fibrosis and, in mouse models, decompresses tumour vessels and improves drug delivery. A single-arm phase 2 (Massachusetts General Hospital) adding losartan to FOLFIRINOX and chemoradiation in locally advanced pancreatic cancer reported a high R0 resection rate, and a randomised phase 2 with added immunotherapy has followed. Losartan is off patent and costs a few dollars a month. The proposal is a publicly funded randomised phase 3 of losartan plus standard neoadjuvant therapy versus standard therapy alone in borderline resectable and locally advanced pancreatic cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":["emt"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-tme-immunosuppression"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding losartan to neoadjuvant chemotherapy increases the R0 resection rate by at least 15 absolute percentage points and improves overall survival in locally advanced pancreatic cancer.","rationale":"Stromal desmoplasia is the defining obstacle in pancreatic cancer and many expensive stroma-targeting agents have failed; losartan's mechanism is supported by imaging and tissue data in patients, and its safety is well known.","test":"Randomised phase 3 of roughly 400 patients with R0 resection rate and OS endpoints, with imaging biomarkers of tumour perfusion in a sub-study.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},"route":"/ideas/idea-reg-losartan-pancreatic-stroma/","neighbours":{"cancer":[{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"}],"pathway":[{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"}],"paper":[{"id":"paper-pantziarka-ecancermedicalscience","kind":"paper","name":"The Repurposing Drugs in Oncology (ReDO) Project","route":"/key-papers/paper-pantziarka-ecancermedicalscience/"}]}}