{"entity":{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","aka":[],"tldr":"Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes.","summary":"Radioligand therapy kills by DNA damage, so blocking repair should amplify it. Early-phase studies combine 177Lu-PSMA with olaparib in prostate cancer and 177Lu-DOTATATE with PARP inhibitors in neuroendocrine tumours; the recurring question is whether marrow toxicity rises faster than tumour control. No phase 3 had read out by 2026.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: Lu-177 PSMA plus olaparib","url":"https://clinicaltrials.gov/search?term=lutetium%20PSMA%20olaparib"}],"tags":["frontier","promising"],"related":[],"cancers":["prostate","neuroendocrine"],"sections":["radiopharma","targeted-therapy"],"technologies":["radioligand-therapy","parp-inhibitor","targeted-alpha-therapy"],"targets":["parp","psma","sstr2","atr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Beta or alpha decay produces single- and double-strand breaks; PARP or ATR inhibition prevents repair, converting sublethal damage into cell death and lowering the activity required.","strengths":["Rational and mechanism-driven","Both components already approved separately","Could reduce the number of radioligand cycles"],"limitations":["Overlapping haematologic toxicity","Optimal sequencing and timing unknown","No randomised evidence yet"]},"route":"/technologies/radionuclide-parp-combination/","neighbours":{"cancer":[{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"radiopharma","kind":"section","name":"Radiopharmaceuticals & Theranostics","route":"/fronts/radiopharma/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"atr","kind":"target","name":"ATR","route":"/targets/atr/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"},{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"},{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"roadmap":[{"id":"cure-paths","kind":"roadmap","name":"Paths to cures: interception, eradication, control","route":"/roadmaps/cure-paths/"},{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"},{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}],"pathway":[{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"}]}}