ArticleCancer research2014
Targeting PARP-1 allosteric regulation offers therapeutic potential against cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- A Phase I/II Study of Veliparib (ABT-888) in Combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Trial
- Bone sialoprotein: a multifunctional regulator of bone remodelling and tumour progression.Bone research · 2026Review
- Preclinical studies of a PARP-targeted theranostic radiopharmaceutical for pancreatic cancer.Frontiers in pharmacology · 2025Article
- USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity.Science advances · 2024Article
- Article
- The dynamics and regulation of PARP1 and PARP2 in response to DNA damage and during replication.DNA repair · 2024Review
- Donor-Acceptor Pyridinium Salts for Photo-Induced Electron-Transfer-Driven Modification of Tryptophan in Peptides, Proteins, and Proteomes Using Visible Light.Journal of the American Chemical Society · 2022Article
- Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones.Nature communications · 2021Article
- Combinatorial Efficacy of Olaparib with Radiation and ATR Inhibitor Requires PARP1 Protein in Homologous Recombination-Proficient Pancreatic Cancer.Molecular cancer therapeutics · 2021Article
- Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo.Nucleic acids research · 2020Article
- Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib.Journal of translational medicine · 2020Article
- Allostery in Its Many Disguises: From Theory to Applications.Structure (London, England : 1993) · 2019Review
- PARP family enzymes: regulation and catalysis of the poly(ADP-ribose) posttranslational modification.Current opinion in structural biology · 2018Review
- Article
- PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs.International journal of molecular sciences · 2017Review
- PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes.Genes & development · 2017Review
- Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic.Journal of experimental & clinical cancer research : CR · 2016Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
PARP-1 is a nuclear protein that has important roles in maintenance of genomic integrity. During genotoxic stress, PARP-1 recruits to sites of DNA damage where PARP-1 domain architecture initiates catalytic activation and subsequent poly(ADP-ribose)-dependent DNA repair. PARP-1 inhibition is a promising new way to selectively target cancers harboring DNA repair deficiencies. However, current inhibitors target other PARPs, raising important questions about long-term off-target effects. Here, we propose a new strategy that targets PARP-1 allosteric regulation as a selective way of inhibiting PARP-1. We found that disruption of PARP-1 domain-domain contacts through mutagenesis held no cellular consequences on recruitment to DNA damage or a model system of transcriptional regulation, but prevented DNA-damage-dependent catalytic activation. Furthermore, PARP-1 mutant overexpression in a pancreatic cancer cell line (MIA PaCa-2) increased sensitivity to platinum-based anticancer agents. These results not only highlight the potential of a synergistic drug combination of allosteric PARP inhibitors with DNA-damaging agents in genomically unstable cancer cells (regardless of homologous recombination status), but also signify important applications of selective PARP-1 inhibition. Finally, the development of a high-throughput PARP-1 assay is described as a tool to promote discovery of novel PARP-1 selective inhibitors.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.