ArticlePediatric blood & cancer2014
Preclinical evaluation of the PARP inhibitor, olaparib, in combination with cytotoxic chemotherapy in pediatric solid tumors.
Article in Pediatric blood & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma.Cell reports. Medicine · 2026Article
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors.Cancer chemotherapy and pharmacology · 2026Article
- BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.NPJ precision oncology · 2026Article
- Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.Discover oncology · 2026Review
- Tumor suppressor network dysregulation in neuroblastoma: molecular mechanisms and precision therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- RSL3 promotes PARP1 apoptotic functions by distinct mechanisms during ferroptosis.Cellular & molecular biology letters · 2025Article
- Complete remission with olaparib in BRIP1-mutated metastatic high-grade pleomorphic sarcoma: case study and literature review - an example of a genomic profiling-based tumor treatment, in a cancer type with high unmet clinical need.Acta oncologica (Stockholm, Sweden) · 2025Review
- Identifying Molecular Probes for Fluorescence-Guided Surgery in Neuroblastoma: A Systematic Review.Children (Basel, Switzerland) · 2025Review
- Alternative lengthening of telomere-based immortalization renders H3G34R-mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.Neuro-oncology · 2025Article
- Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas.Frontiers in oncology · 2024Review
- Mixed effects modeling of radiotherapy in combination with immune checkpoint blockade or inhibitors of the DNA damage response pathway.CPT: pharmacometrics & systems pharmacology · 2023Article
- Article
- NKp44-Derived Peptide Used in Combination Stimulates Antineoplastic Efficacy of Targeted Therapeutic Drugs.International journal of molecular sciences · 2022Article
- A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers.Frontiers in pharmacology · 2022Article
- Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response.Frontiers in endocrinology · 2022Article
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy.Acta pharmaceutica Sinica. B · 2021Review
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.EBioMedicine · 2020Article
Corrections and comments
- Erratum issuedCORRIGENDUM.2021
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPoly(ADP-ribose) polymerase (PARP) signals DNA damage and facilitates DNA repair. PARP inhibitors are being evaluated in cancers with defective DNA repair mechanisms or in combination with cytotoxic therapy or radiation. We evaluated the PARP inhibitor, olaparib, in combination with chemotherapy using in vitro and in vivo pediatric solid tumor models. PROCEDURE: The IC50 of olaparib alone and in combination with cytotoxic agents was determined in 10 pediatric solid tumor cell lines. Synergy was assessed using the combination index of Chou-Talalay. Olaparib alone and in combination with topotecan/cyclophosphamide was evaluated in xenograft models of Ewing sarcoma (RD-ES) and neuroblastoma (NGP). PAR activity was evaluated in cell lines and tumor lysates.
resultsOlaparib induced growth inhibition, median (range) IC50 = 3.6 (1-33.8) µM, and inhibited PAR activity in pediatric solid tumor cell lines. The addition of olaparib to DNA damaging agents resulted in additive to synergistic interactions. In RD-ES and NGP xenografts, olaparib inhibited PAR activity by 88-100% as a single agent and 100% when administered with cyclophosphamide/topotecan. Although the addition of olaparib did not antagonize the activity of cyclophosphamide/topotecan, clear evidence of synergy could not be demonstrated.
conclusionsIn pediatric solid tumor cell lines, clinically achievable concentrations of single agent olaparib caused growth inhibition. Although the in vitro data demonstrated synergistic efficacy of olaparib when added to the camptothecins and alkylating agents, synergy was not discernible in vivo. Clinical trials of PARP inhibitors in combination DNA damaging agents are necessary to establish the role of PARP inhibitors in childhood cancer.
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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.