ArticlePloS one2018
ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- A multi-site phase I trial of Veliparib with standard radiation and temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).Journal of neuro-oncology · 2023Trial
- Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.AJNR. American journal of neuroradiology · 2020Trial
- Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2'-deoxyuridine (EdU).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Combinatorial Treatment of Glioblastoma with Temozolomide (TMZ) Plus 5-Ethynyl-2'-deoxyuridine (EdU).bioRxiv : the preprint server for biology · 2025Article
- Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.Cancers · 2024Review
- Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024Review
- Mitogen-induced defective mitosis transforms neural progenitor cells.Neuro-oncology · 2023Article
- Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer.Cancer research communications · 2023Article
- The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors.Current treatment options in oncology · 2022Review
- Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.Cancers · 2022Review
- An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma.Frontiers in genetics · 2022Article
- PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma.Neuro-oncology · 2021Article
- Review
- Contemporary Mouse Models in Glioma Research.Cells · 2021Review
- siRNA nanoparticle suppresses drug-resistant gene and prolongs survival in an orthotopic glioblastoma xenograft mouse model.Advanced functional materials · 2021Article
- MGMT promoter methylation and hypermutant recurrence in IDH mutant lower-grade glioma.Neuro-oncology · 2020Article
- In vitro modeling of glioblastoma initiation using PDGF-AA and p53-null neural progenitors.Neuro-oncology · 2020Article
- Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance.International journal of molecular sciences · 2020Review
- PARP inhibition suppresses the emergence of temozolomide resistance in a model system.Journal of neuro-oncology · 2020Article
- Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTemozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ.
methodsUsing patient derived brain tumor initiating cells (BTICs) and orthotopic xenografts as models of newly diagnosed and recurrent high-grade glioma, we assessed the effects of TMZ, ABT-888, and the combination of TMZ and ABT-888 on the viability of BTICs and survival of tumor-bearing mice. We also studied DNA damage repair, checkpoint protein phosphorylation, and DNA replication in mismatch repair (MMR) deficient cells treated with TMZ and TMZ plus ABT-888.
resultsCells and xenografts derived from newly diagnosed MGMT methylated high-grade gliomas were sensitive to TMZ while those derived from unmethylated and recurrent gliomas were typically resistant. ABT-888 had no effect on the viability of BTICs or tumor bearing mice, but co-treatment with TMZ restored sensitivity in resistant cells and xenografts from newly diagnosed unmethylated gliomas and recurrent gliomas with MSH6 mutations. In contrast, the addition of ABT-888 to TMZ had little sensitizing effect on cells and xenografts derived from newly diagnosed methylated gliomas. In a model of acquired TMZ resistance mediated by loss of MMR gene MSH6, re-sensitization to TMZ by ABT-888 was accompanied by persistent DNA strand breaks, re-engagement of checkpoint kinase signaling, and interruption of DNA synthesis.
conclusionIn laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ.
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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.