Genome-wide CRISPR/Cas9 knock-out screens in BRCA1/2-proficient prostate cancer (PC) cells identified genes whose loss has a profound impact on PARPis response and find that loss of Checkpoint Kinase 2 (CHEK2), which is involved in the DNA damage repair response, confers PARPis resistance in PC cells with functional p53 [68], and that deletion of Ribonuclease H2 Subunit B (RNASEH2B), which play a role in DNA replication, confers PC cell sensitivity to PARPis [69]. This evidence concerns the gene BRCA1 and pachyonychia congenita.