ArticleMolecular cancer therapeutics2015
Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- The Enemy of My Enemy: Two Cases of De Novo Metastatic Small-Cell Neuroendocrine Prostate Cancer with BRCA2 Alterations and Brain Metastases.International journal of molecular sciences · 2026Article
- Folic Acid-Guided PLGA-Zein Core-Shell Nanoparticles for Co-Delivery of Temozolomide and Ellagic Acid to Overcome PARP-Mediated Chemoresistance in Glioblastoma.Pharmaceutics · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Assessment of brain penetration and tumor accumulation of niraparib and olaparib: insights from multimodal imaging in preclinical models.Scientific reports · 2025Article
- Review
- Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Olaparib: A Chemosensitizer for the Treatment of Glioblastoma.Mini reviews in medicinal chemistry · 2025Review
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- The Glioblastoma Landscape: Hallmarks of Disease, Therapeutic Resistance, and Treatment Opportunities.Medical research archives · 2023Article
- Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.Clinical pharmacokinetics · 2022Review
- Imaging PARP with [European journal of nuclear medicine and molecular imaging · 2022Article
- Nanotechnology-Based Combinatorial Anti-Glioblastoma Therapies: Moving from Terminal to Treatable.Pharmaceutics · 2022Review
- Prostate Cancer Brain Metastasis: Review of a Rare Complication with Limited Treatment Options and Poor Prognosis.Journal of clinical medicine · 2022Review
- A Novel Classification Model for Lower-Grade Glioma Patients Based on Pyroptosis-Related Genes.Brain sciences · 2022Article
- Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors.Cell reports · 2022Article
- P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhiitor Ensartinib in Cancer Cells.Cancers · 2022Article
- Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.Cancers · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b(-/-)Bcrp1(-/-) knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM.
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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.