Abstract：
:Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination. Five PARP inhibitors are now in late-stage development in clinical trials that are seeking to expand the understanding of targeted therapies and DNA repair defects in human cancer. This review examines the cell biology of PARP, the discovery of synthetic lethality with HR deficiency, the clinical development of PARP inhibitors, and the role of PARP inhibitors in ongoing clinical trials and clinical practice.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Dulaney C,Marcrom S,Stanley J,Yang ESdoi
10.1016/j.semcdb.2017.01.007subject
Has Abstractpub_date
2017-03-01 00:00:00pages
144-153eissn
1084-9521issn
1096-3634pii
S1084-9521(17)30009-5journal_volume
63pub_type
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