BRCA1 and cancer: Their clinical benefit for the treatment of various cancers, in particular breast and ovarian cancers with mutations in BRCA1 or BRCA2 (breast cancer type 1 and 2 susceptibility proteins) largely relies on a principle called ‘synthetic lethality,’ a concept in which defects in one gene have minimal effects on cells, but defects in a combination of genes are cell-lethal.6 PARP inhibitors trap PARP onto the DNA and subsequently cause DNA replication-associated DNA double-strand breaks.