Since first described in 200512,13, PARPi have been shown to exert synthetic lethality in HR-deficient tumor cells via multiple mechanisms, including inhibiting base excision repair (BER), trapping of PARP–DNA complexes, activating error-prone non-homologous end joining (NHEJ), and interfering with PARP1/POLQ-mediated alternative end joining (alt-EJ)14,15. The gene discussed is PARP1; the disease is neoplasm.