While there is a substantial body of work that has identified genetic mechanisms of PARPi resistance, including genetic disruption of the Shieldin complex components and spontaneous BRCA1 reversion mutations, less work has been published to isolate synthetic lethal targets using isogenic cell lines with stable genetic deletions or reversions with BRCA1, which is the context in which most cancers will need to be treated. This evidence concerns the gene BRCA1 and cancer.