BRCA2 and cancer: In contrast to the above-mentioned targeted therapies that rely on mutations/amplifications in a single gene for identification of patients likely to benefit, PARP inhibitors work more indirectly by synthetic lethality in patients with mutated BRCA1 or BRCA2. 17, 18 Both BRCA1 and BRCA2 are key components of the homologous recombination (HR) double-stranded break DNA repair pathway, resulting in increased risk of developing breast, ovarian, lung, bladder, and other cancers if they are mutated.