{"entity":{"id":"mechanobiology-therapy","kind":"technology","name":"Targeting tumour mechanics and pressure","aka":[],"tldr":"Stiff, high-pressure tumours squeeze their own blood vessels shut, keeping drugs out. Softening them is a way in.","summary":"Desmoplastic tumours such as pancreatic cancer generate solid stress that collapses vessels; agents that reduce matrix stiffness (losartan, hyaluronidase, LOXL2 inhibitors) aim to reopen perfusion. PEGPH20, the furthest-advanced hyaluronidase, failed its phase 3 in pancreatic cancer, and losartan combinations remain investigational. The physics is well characterised; converting it into benefit has so far failed.","status":"preclinical","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: losartan pancreatic cancer","url":"https://clinicaltrials.gov/search?term=losartan%20pancreatic%20cancer"}],"tags":["frontier"],"related":[],"cancers":["pancreatic"],"sections":["targeted-therapy","drug-discovery"],"technologies":["cytotoxic-chemotherapy","antiangiogenic","single-cell-spatial"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Reducing extracellular matrix content or stiffness lowers solid stress, decompresses vessels, and improves delivery of drugs and immune cells.","strengths":["Addresses a delivery barrier shared by the tumours with the lowest survival","Cheap existing agents to test","Measurable with imaging"],"limitations":["PEGPH20 phase 3 failure","Loosening the matrix may aid invasion","No demonstrated effect on outcomes"]},"route":"/technologies/mechanobiology-therapy/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"}],"roadmap":[{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"}]}}