Pharmacological inhibition of key proteins involved in the response to DNA damage has emerged as an e ective tool for cancer treatment, as the resistance of cancer cells to DNA-damaging agents originates from the modulation of DNA repair pathways. PARP has important pro-survival and protective functions in terms of DNA repair. A multitude of novel pharmacological inhibitors of PARP has entered clinical testing either as adjunct antitumor therapeutics or as monotherapy in familiar breast and ovarian cancer. Besides the antineoplasic action of PARP inhibitors, the evidence summarized above strongly supports a crucial role of the ROS/NF-kB/PARP pathway in mediating multiple in ammatory diseases including type I diabetes and associated endothelial dysfunction, cardiovascular injury and heart failure, sepsis, rheumatoid arthritis and stroke. e information available to date supports the view that PARP over-activation during in ammatory damage is a pivotal feature of tissue damage in di erent in ammatory-based pathologies, and that the pharmacological inhibition of PARP may provide signi cant bene ts in these conditions by salvaging a ected tissues from necrosis, and by reducing, as well as by downregulating, the in ammatory responses. As with all new
therapeutic areas, the usefulness of this target is unproven, but the potential e ect of this class of agents is large. Whereas the clinical bene t of PARP inhibitors is being tested, additional new areas of research are also opening up in the preclinical front, which should eventually help in the consecution of new and more e ective PARP inhibitors able to regulate the ne tuning of this pathway, including the speci c inhibition of di erent PARP members, the association of PARP-1 in di erent complexes, and the activation/inactivation of poly(ADP-glycohydrolase).