Advances in using PARP inhibitors to treat cancer

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

• Publication year

  2012

• Venue

  BMC Medicine

• Publication date

  2012-03-09

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/1741-7015-10-25PMID 22401667PMCID 3312820
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer.

  2012cited by this paper
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  2011cited by this paper
• Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial

  2011cited by this paper
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  2011cited by this paper
• Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study.

  2011cited by this paper
• Integrated Genomic Analyses of Ovarian Carcinoma

  2011cited by this paper
• Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations

  2011cited by this paper
• Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).

  2011cited by this paper
• Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas.

  2011cited by this paper
• Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells

  2011cited by this paper
• Challenges to the development of new agents for molecularly defined patient subsets: lessons from BRCA1/2-associated breast cancer.

  2011cited by this paper
• PARP inhibition: PARP1 and beyond

  2010cited by this paper
• Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate

  2010cited by this paper
• First-in-human trial of a poly(ADP)-ribose polymerase (PARP) inhibitor MK-4827 in advanced cancer patients with antitumor activity in BRCA-deficient tumors and sporadic ovarian cancers (soc).

  2010cited by this paper
• Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial.

  2010cited by this paper
• Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130

  2010cited by this paper
• 362 First in human trial of a poly(ADP)-ribose polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (p) with antitumor activity in BRCA-deficient and sporadic ovarian cancers

  2010cited by this paper
• PHASE II STUDY OF THE ORAL PARP INHIBITOR OLAPARIB (AZD2281) VERSUS LIPOSOMAL DOXORUBICIN IN OVARIAN CANCER PATIENTS WITH BRCA1 AND/OR BRCA2 MUTATIONS

  2010cited by this paper
• Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial.

  2010cited by this paper
• A phase I combination study of olaparib (AZD2281; KU-0059436) and cisplatin (C) plus gemcitabine (G) in adults with solid tumors.

  2010cited by this paper
• Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.

  2010cited by this paper
• Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial.

  2010cited by this paper
• Synthetic lethality--a new direction in cancer-drug development.

  2009cited by this paper
• Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.

  2009cited by this paper
• Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors

  2009cited by this paper
• Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns

  2009cited by this paper
• Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.

  2009cited by this paper
• Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies of Mouse Xenografts

  2008cited by this paper
• PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways

  2006cited by this paper
• Mental health and resiliency following 44 months of terrorism: a survey of an Israeli national representative sample

  2006cited by this paper
• Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

  2005cited by this paper
• How does a cell repair damaged DNA?

  2005cited by this paper
• Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

  2005cited by this paper
• (ADP-ribose)n participates in DNA excision repair

  1980cited by this paper
• Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme.

  1963cited by this paper

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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
• Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma

  2023cites this paper
• A Review on Poly (ADP-ribose) Polymerase (PARP) - An Enzyme that Share the ability to Catalyze the Transfer of ADP-Ribose to Target Proteins

  2023cites this paper
• Roles of DNA damage repair and precise targeted therapy in renal cancer (Review)

  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019influential citation
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  2019influential citation
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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