PARP1 and cancer: However, I believe PARP inhibition in HRD is unlikely to be bettered as an example of synthetic lethality for 2 reasons: (1) there is a very high level of DNA SSB, that depend on PARP for their repair, due to the endogenous ROS produced by normal metabolism, and this is increased in cancer by virtue of the associated inflammation, and (2) HRR defects are relatively common in cancer, not only due to BRCA mutations.