Journal
FRONTIERS IN ONCOLOGY
Volume 3, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2013.00290
Keywords
PARP-1; PARP inhibitors; NF-kappa B; genetic transcription; sex hormone signaling; ERK signaling; angiogenesis; mitotic spindle
Categories
Funding
- Department of Defense
- American Association of Cancer Research
- NIH-National Institute of General Medical Sciences [5T32GM008361-21]
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Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that transfer negatively charged ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide (NADT) to a variety of protein substrates, altering protein protein and protein-DNA interactions. The most studied of these enzymes is poly(ADP-ribose) polymerase-1 (PARP-1), which is an excellent therapeutic target in cancer due to its pivotal role in the DNA damage response. Clinical studies have shown susceptibility to PARP inhibitors in DNA repair defective cancers with only mild adverse side effects. Interestingly, additional studies are emerging which demonstrate a role for this therapy in DNA repair proficient tumors through a variety of mechanisms. In this review, we will discuss additional functions of PARP-1 including regulation of inflammatory mediators, cellular energetics and death pathways, gene transcription, sex hormone-and ERK-mediated signaling, and mitosis and the role these PARP-1-mediated processes play in oncogenesis, cancer progression, and the development of therapeutic resistance. As PARP-1 can act in both a pro-and anti-tumor manner depending on the context, it is important to consider the global effects of this protein in determining when, and how, to best use PARP inhibitors in anticancer therapy.
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