By interfering with efficient DNA damage repair, the inhibition of PARP that target the base excision repair (BER) pathway leads to insufficient DNA repair, with subsequent unsustainable DNA damage, and thus represents a synthetic lethal therapeutic approach for the treatment of cancers with compromised ability to repair double-strand DNA breaks by homologous recombination (HR), including those with defects in BRCA1/2 [30]. The gene discussed is PARP1; the disease is cancer.