{"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":["lu-177"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["parp","psma","sstr2"],"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":{"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"indication":[{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"technology":[{"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":"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/"}],"idea":[{"id":"idea-rlt-plus-parp-inhibitor","kind":"idea","name":"Adding a PARP inhibitor to PSMA radioligand therapy","route":"/ideas/idea-rlt-plus-parp-inhibitor/"}],"pairing":[{"id":"pluvicto-plus-olaparib","kind":"pairing","name":"177Lu-PSMA-617 (Pluvicto) with olaparib","route":"/pairings/pluvicto-plus-olaparib/"}]}}