# Radioligand plus DNA-repair inhibitor combinations

Source: https://onco.cc/technologies/radionuclide-parp-combination/  
OnCo record `radionuclide-parp-combination` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-1
- Last checked: 2026-09-08
- Tags: frontier; promising
- 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

## Sources

- ClinicalTrials.gov: Lu-177 PSMA plus olaparib: https://clinicaltrials.gov/search?term=lutetium%20PSMA%20olaparib

## Connected records

- cancers: [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Radiopharmaceuticals & Theranostics](https://onco.cc/fronts/radiopharma/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/), [Targeted alpha therapy](https://onco.cc/technologies/targeted-alpha-therapy/)
- targets: [ATR](https://onco.cc/targets/atr/), [PARP](https://onco.cc/targets/parp/), [PSMA](https://onco.cc/targets/psma/), [Somatostatin receptor 2](https://onco.cc/targets/sstr2/)
- roadmaps: [Paths to cures: interception, eradication, control](https://onco.cc/roadmaps/cure-paths/), [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/)
- pathways: [Base excision repair, PARP & alkylation damage](https://onco.cc/pathways/base-excision-repair-parp/)

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