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Nature Reviews Clinical Oncology, 2020
The much anticipated results from two phase III studies evaluating the clinical efficacy of poly(ADP-ribose) polymerase (PARP) inhibition in patients with advanced-stage breast cancer harbouring a germline mutation in BRCA1/2 have established new therapeutic opportunities and yet, have left us with several ongoing questions.
Shani Paluch-Shimon, Fatima Cardoso
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The much anticipated results from two phase III studies evaluating the clinical efficacy of poly(ADP-ribose) polymerase (PARP) inhibition in patients with advanced-stage breast cancer harbouring a germline mutation in BRCA1/2 have established new therapeutic opportunities and yet, have left us with several ongoing questions.
Shani Paluch-Shimon, Fatima Cardoso
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Mechanisms of PARP Inhibitor Resistance
2023Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) represent the first medicines based on the targeting of the DNA damage response (DDR). PARPi have become standard of care for first-line maintenance treatment in ovarian cancer and have also been approved in other cancer indications including breast, pancreatic and prostate.
Mark J, O'Connor, Josep V, Forment
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PARP inhibitor resistance mechanisms and PARP inhibitor derived imaging probes
Expert Review of Anticancer TherapyPoly(ADP-ribose) polymerase 1 (PARP1) inhibition has become a major target in anticancer therapy. While PARP inhibitors (PARPi) are approved for homologous recombination (HR) deficient cancers, therapeutic resistance is a challenge and PARPi are now being investigated in cancers lacking HR deficiencies.
Tony, Yu, Benjamin H, Lok
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IDrugs : the investigational drugs journal, 2005
Poly(ADP-ribose) polymerase (PARP) catalyzes the biochemical conversion of nicotinamide adenine dinucleotide (NAD+) to poly(ADP-ribose) and nicotinamide, which is a weak feedback inhibitor of the enzyme. Early designs of PARP inhibitors were primarily based on mimicking the structure of nicotinamide and resulted in the identification and widespread use
J H, Li, J, Zhang
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Poly(ADP-ribose) polymerase (PARP) catalyzes the biochemical conversion of nicotinamide adenine dinucleotide (NAD+) to poly(ADP-ribose) and nicotinamide, which is a weak feedback inhibitor of the enzyme. Early designs of PARP inhibitors were primarily based on mimicking the structure of nicotinamide and resulted in the identification and widespread use
J H, Li, J, Zhang
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Nature Biotechnology, 2012
A comprehensive study of ligand binding to the human PARP family of proteins reveals the molecular basis of inhibitor selectivity and promiscuity.
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A comprehensive study of ligand binding to the human PARP family of proteins reveals the molecular basis of inhibitor selectivity and promiscuity.
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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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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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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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