The Role of PARP and the Therapeutic Potential of PARP Inhibitors in Cancer
PARP1 is the founder and most abundant of a superfamily of 17 enzymes, it plays a key role in the repair of DNA single-strand breaks, the most common form of endogenous DNA damage. PARP inhibitors were first developed to inhibit DNA repair and resistance to DNA damaging anticancer therapy. In 2005 two landmark papers were published showing that PARP inhibitors as single agents selectively kill cells lacking homologous recombination DNA repair, including those with BRCA1 or BRCA2 mutations. Four PARP inhibitors are now approved for the treatment of cancer: 3 for ovarian cancer, 2 for breast cancer 2 for metastatic castrate-resistant prostate cancer and 1 for pancreatic cancer with other tumour types under investigation. This chapter describes the journey from identification of the enzyme to the present day.