BRCA1 and cancer: Pre- and post-platinum progressionpaired biopsies of EOC have shown that the de-silencing ofBRCA1 is linked to platinum resistance.54 Asdemonstrated in patient-derived xenograft (PDX) models of PARPi-resistantbreast cancer, the loss of BRCA1 promoter methylationrestores functional BRCA1 expression to the levels found inHR-proficient tumors.42 In EOC,susceptibility to PARPi was subsequently found to requireBRCA1 silencing by homozygous methylation of all copiespresent in the gene.55 Loss of promotermethylation of even one copy of BRCA1 (heterozygousmethylation) resulted in PARPi resistance.42