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PARP inhibitors for cancer therapy
Expert Reviews in Molecular Medicine, 2005Poly(ADP-ribose) polymerase 1 (PARP-1) is a zinc-finger DNA-binding enzyme that is activated by binding to DNA breaks. Poly(ADP-ribosyl)ation of nuclear proteins by PARP-1 converts DNA damage into intracellular signals that activate either DNA repair by the base-excision pathway or cell death. A family of 18 PARPs has been identified, but only the most
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Clinical perspectives of PARP inhibitors
Pharmacological Research, 2005Poly(ADP-ribose) polymerase (PARP) activation plays a role in the pathogenesis of various cardiovascular and inflammatory diseases. At the same time, PARP activation is also relevant for the ability of cells to repair injured DNA. Thus, depending on the circumstances, pharmacological inhibitors of PARP may be able to attenuate ischemic and inflammatory
GRAZIANI, GRAZIA, Szabo C.
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PARP inhibitors for anticancer therapy
Biochemical Society Transactions, 2014PARP-1 [poly(ADP-ribose) polymerase-1], which plays a key role in DNA repair, was discovered 50 years ago. PARPi (PARP inhibitors), originally made to probe the function of the enzyme, inhibit DNA repair and increase the potency of anticancer cytotoxic agents.
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PARP Inhibitors in Prostate Cancer
Current Treatment Options in Oncology, 2017The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown
Praveen, Ramakrishnan Geethakumari +3 more
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PARP Inhibitors and Parkinson’s Disease
New England Journal of Medicine, 2019PARP Inhibitors and Parkinson’s Disease A recent study implicates the enzyme poly(adenosine 5′-diphosphate-ribose) polymerase 1 (PARP1) as a mediator of neuronal cell death in Parkinson’s disease.
Abby L, Olsen, Mel B, Feany
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2016
Inhibition of Poly (ADP-ribose) polymerase 1 has relatively recently entered the clinic. The ground-breaking drug both scientifi cally and clinically was olaparib, but several other PARP inhibitors are in development. This treatment is the fi rst to therapeutically exploit mutant recessive cancer genes.
Grève, J.De +8 more
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Inhibition of Poly (ADP-ribose) polymerase 1 has relatively recently entered the clinic. The ground-breaking drug both scientifi cally and clinically was olaparib, but several other PARP inhibitors are in development. This treatment is the fi rst to therapeutically exploit mutant recessive cancer genes.
Grève, J.De +8 more
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A snapshot of chemoresistance to PARP inhibitors
Trends in Pharmacological Sciences, 2012The exploitation of synthetic lethality in BRCA-deficient tumor carriers using potent inhibitors of the enzyme poly(ADP-ribose) polymerase (PARP)-1 has led to an enthusiastic response among basic scientists, oncologists and pharmaceutical companies. However, accumulating evidence demonstrates that resistance to these drugs develops in tumors in both ...
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PARP inhibitors in ovarian cancer
Seminars in OncologyPoly-ADP-ribose polymerase inhibitors (PARPis) were first approved for the treatment of epithelial ovarian cancer (EOC), where as a maintenance therapy they transformed clinical management of this disease in both patients with and without homologous recombination deficiency.
Ian S. Goldlust +2 more
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