The demonstration that BRCA1 and BRCA2 mutant human cancer cell lines and tumour xenografts are exquisitely sensitive to small-molecule inhibitors of poly (ADP-ribose) polymerase (PARP) was critical for the clinical development and approval of PARP inhibitors as single agents and provided the first clinical exemplification of synthetic lethality in oncology13,14. This evidence concerns the gene PARP1 and cancer.