{"entity":{"id":"hypoxia-activated-therapy","kind":"technology","name":"Hypoxia-activated prodrugs","aka":[],"tldr":"A harmless molecule that turns into a poison only where there is no oxygen, which in the body means inside a tumour.","summary":"Tumour cores are hypoxic in a way normal tissue is not, so a prodrug reduced only under low oxygen should be tumour-selective. Evofosfamide failed two phase 3 trials in 2015; the field has since focused on better patient selection using hypoxia imaging or gene signatures, and on newer scaffolds. It remains a clean idea with a poor clinical record.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: hypoxia-activated prodrug","url":"https://clinicaltrials.gov/search?term=hypoxia-activated%20prodrug"}],"tags":["frontier"],"related":[],"cancers":["pancreatic","sarcoma"],"sections":["chemotherapy","targeted-therapy"],"technologies":["cytotoxic-chemotherapy","imrt-igrt","fdg-pet","antiangiogenic"],"targets":["hif2a"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"One-electron reduction of a nitroaromatic or quinone trigger is reversed by oxygen; where oxygen is absent, fragmentation releases an active cytotoxin.","strengths":["Exploits a difference no normal tissue shares","Kills the hypoxic cells radiotherapy misses","Combines with radiation and antiangiogenics"],"limitations":["Two phase 3 failures without hypoxia selection","Needs a validated hypoxia biomarker","The prodrug must diffuse into a poorly perfused region"]},"route":"/technologies/hypoxia-activated-therapy/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"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":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"target":[{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"}],"roadmap":[{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"}],"pathway":[{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"angiogenic-switch","kind":"pathway","name":"The angiogenic switch & tumour vessels","route":"/pathways/angiogenic-switch/"}],"company":[{"id":"threshold-pharmaceuticals","kind":"company","name":"Threshold Pharmaceuticals","route":"/companies/threshold-pharmaceuticals/"}]}}