Radioligand plus DNA-repair inhibitor combinations
Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes.
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.
How it works
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.
- Rational and mechanism-driven
- Both components already approved separately
- Could reduce the number of radioligand cycles
- Overlapping haematologic toxicity
- Optimal sequencing and timing unknown
- No randomised evidence yet
Latest papers
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