ArticleThe Journal of biological chemistry2014
Poly(ADP-ribose) polymerase inhibitors sensitize cancer cells to death receptor-mediated apoptosis by enhancing death receptor expression.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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.
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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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma.Frontiers in oncology · 2022Pooled it
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- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
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- Biomarkers related to m6A and succinic acid metabolism in papillary thyroid carcinoma.BMC medical genomics · 2024Article
- PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer.Genes and immunity · 2024Article
- Gasdermin C sensitizes tumor cells to PARP inhibitor therapy in cancer models.The Journal of clinical investigation · 2024Article
- Therapeutic targeting of PARP with immunotherapy in acute myeloid leukemia.Frontiers in pharmacology · 2024Review
- Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses.Pharmaceutics · 2023Article
- Polyadenosine diphosphate-ribose polymerase inhibitors: advances, implications, and challenges in tumor radiotherapy sensitization.Frontiers in oncology · 2023Review
- Review
- TRAIL Receptor Targeting Agents Potentiate PARP Inhibitor Efficacy in Pancreatic Cancer Independently ofCancers · 2022Article
- Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.Journal of hematology & oncology · 2022Review
- Improving PARP inhibitor efficacy in high-grade serous ovarian carcinoma: A focus on the immune system.Frontiers in genetics · 2022Review
- Review
- Review
- PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome.Blood advances · 2021Review
- Targeting the DNA damage response in immuno-oncology: developments and opportunities.Nature reviews. Cancer · 2021Review
- Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Recombinant human tumor necrosis factor-α-related apoptosis inducing ligand (TRAIL), agonistic monoclonal antibodies to TRAIL receptors, and small molecule TRAIL receptor agonists are in various stages of preclinical and early phase clinical testing as potential anticancer drugs. Accordingly, there is substantial interest in understanding factors that affect sensitivity to these agents. In the present study we observed that the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and veliparib sensitize the myeloid leukemia cell lines ML-1 and K562, the ovarian cancer line PEO1, non-small cell lung cancer line A549, and a majority of clinical AML isolates, but not normal marrow, to TRAIL. Further analysis demonstrated that PARP inhibitor treatment results in activation of the FAS and TNFRSF10B (death receptor 5 (DR5)) promoters, increased Fas and DR5 mRNA, and elevated cell surface expression of these receptors in sensitized cells. Chromatin immunoprecipitation demonstrated enhanced binding of the transcription factor Sp1 to the TNFRSF10B promoter in the presence of PARP inhibitor. Knockdown of PARP1 or PARP2 (but not PARP3 and PARP4) not only increased expression of Fas and DR5 at the mRNA and protein level, but also recapitulated the sensitizing effects of the PARP inhibition. Conversely, Sp1 knockdown diminished the PARP inhibitor effects. In view of the fact that TRAIL is part of the armamentarium of natural killer cells, these observations identify a new facet of PARP inhibitor action while simultaneously providing the mechanistic underpinnings of a novel therapeutic combination that warrants further investigation.
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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.