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The Vasoactivity of PARP Inhibitors
2015PARP-inhibition has proven to be an attractive therapeutic approach in cancer whereby the effectiveness of DNA-damaging therapy can be enhanced by inhibiting the PARP-mediated DNA-repair process. Generally there is good concordance between enhanced therapeutic efficacy in vitro and that observed in vivo.
Williams, Kaye J., McCrudden, Cian M.
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Current Breast Cancer Reports, 2011
Poly (ADP-ribose) polymerase (PARP) is a novel therapeutic target in cancer. Preclinical studies demonstrate that PARP inhibitors selectively kill BRCA-deficient cells and potentiate the effects of DNA-damaging agents. There are several PARP inhibitors in clinical development, including olaparib, iniparib, veliparib, PF-01367338, and MK-4827.
Hongyan Liang, Antoinette R. Tan
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Poly (ADP-ribose) polymerase (PARP) is a novel therapeutic target in cancer. Preclinical studies demonstrate that PARP inhibitors selectively kill BRCA-deficient cells and potentiate the effects of DNA-damaging agents. There are several PARP inhibitors in clinical development, including olaparib, iniparib, veliparib, PF-01367338, and MK-4827.
Hongyan Liang, Antoinette R. Tan
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Tackling PARP inhibitor resistance
Trends in Cancer, 2021Homologous recombination-deficient (HRD) tumours, including those harbouring mutations in the BRCA genes, are hypersensitive to treatment with inhibitors of poly(ADP-ribose) polymerase (PARPis). Despite high response rates, most HRD cancers ultimately develop resistance to PARPi treatment through reversion mutations or genetic/epigenetic alterations to
Fugger, Kasper +3 more
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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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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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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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PARP inhibitor combination therapy
Critical Reviews in Oncology/Hematology, 2016In 2014, olaparib (Lynparza) became the first PARP (Poly(ADP-ribose) polymerase) inhibitor to be approved for the treatment of cancer. When used as single agents, PARP inhibitors can selectively target tumour cells with BRCA1 or BRCA2 tumour suppressor gene mutations through synthetic lethality.
Dréan, A, Lord, CJ, Ashworth, A
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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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Development of PARP inhibitors in oncology
Expert Opinion on Investigational Drugs, 2008Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA repair mechanisms by detecting and initiating repair after DNA strand breaks. Inhibition of PARP in DNA repair-defective tumors (like those with BRCA1 or BRCA2 mutations) can lead to gross genomic instability and cell death.
Jordi, Rodon +2 more
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