BRCA1 and cancer: PARPs-induced ADP-ribose marks elevate 10- to 27-fold in response to the oxidative genome damage by H2O2 in human osteosarcoma cells.133,183,184 A variety of cancers have somatic mutations resulting in genomic disability and defective DNA repair, including BRCA1/2, ATM, CHK2 and TP53.395 The loss of double-strand repair pathway due to BRCA1 or BRCA2 mutations renders cancer cells more dependent on the PARPs-mediated repair, and more sensitive to PARP inhibition, raising a possibility of a wider application of PARPi in cancer therapy.396–398