Mutations in the breast cancer type Ⅰ/Ⅱ susceptibility proteins (BRCA1/BRCA2) are associated with hereditary forms of breast, ovarian, pancreatic cancer, fallopian tube, prostate cancer.These hereditary cancers exhibit unstable genomes secondary to defects in DNA damage repair; abnormal centrosome duplication and G2/M cell cycle check point defects.Currently, there is no targeted therapy for these hereditary forms of cancer which are unusually aggressive and generally present lacking both sex hormone and epidermal growth factor receptors.These genetically unstable cancers in order to survive are known to up-regulate the poly(ADP) ribose polymerase enzyme (PARP) up to 500 fold which serves to repair damaged DNA through the base excision repair pathway while also preventing the accidental recombination of homologous DNA.This up regulation of PARP enables survival of the cancer cell and provides resistance to DNA damaging agents used to treat cancer.Recently, it has been shown that BRCA1/2 cancer cells are unusually sensitive to PARP-1 inhibitors.We have that when PARP-1 inhibitors are combined with DNA damaging agents a synergistic kill effect occurs without a significant amount of added toxicity to normal tissue.Furthermore, preliminary evidence suggests that PARP-1 inhibitors may prevent the development of hereditary cancer.Clinical trials are currently underway using PARP-1 inhibitors to treat BRCA 1/2 cancer.