PARP1 and cancer: Although adverse genomic consequences of PARPi therapy have not yet been reported, we need to consider that prolonged PARPi therapy may cause genome instability because PARP-1−/− mouse embryonic fibroblasts have a tendency to become tetraploid (39, 40), and the susceptibility of PARP-1−/− female mice to develop mammary carcinoma is enhanced if p53 is also mutated, a phenomenon frequently observed in cancers (41).