The observation that SHLD2 or MAD2L2 siRNAs caused sensitivity to ART558 in a BRCA1 mutant cell line raised the possibility that a Polθ inhibitor could be used to target PARP inhibitor resistance caused by Shieldin complex defects when these occur in BRCA1 mutant tumour cells. The gene discussed is SHLD2; the disease is neoplasm.