ArticleScientific reports2020
Enhancing Brain Retention of a KIF11 Inhibitor Significantly Improves its Efficacy in a Mouse Model of Glioblastoma.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Review
- Investigation of the role of microtubule on the activity of the mitotic kinesin EG5 using multiscale modelling: unravelling molecular mechanisms.Journal of computer-aided molecular design · 2025Article
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence.iScience · 2024Article
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.Cell reports · 2024Article
- How Much is Enough? Impact of Efflux Transporters on Drug delivery Leading to Efficacy in the Treatment of Brain Tumors.Pharmaceutical research · 2023Review
- Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.bioRxiv : the preprint server for biology · 2023Article
- Improving Localized Radiotherapy for Glioblastoma via Small Molecule Inhibition of KIF11.Cancers · 2023Article
- Article
- Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer.Current cancer drug targets · 2023Article
- H3K27-altered diffuse midline glioma: a paradigm shifting opportunity in direct delivery of targeted therapeutics.Expert opinion on therapeutic targets · 2023Review
- AnPeerJ · 2023Article
- Synergy between inhibitors of two mitotic spindle assembly motors undermines an adaptive response.Molecular biology of the cell · 2022Article
- Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2022Article
- Activation of STAT3 through combined SRC and EGFR signaling drives resistance to a mitotic kinesin inhibitor in glioblastoma.Cell reports · 2022Article
- Central Nervous System Delivery of the Catalytic Subunit of DNA-Dependent Protein Kinase Inhibitor Peposertib as Radiosensitizer for Brain Metastases.The Journal of pharmacology and experimental therapeutics · 2022Article
- Preclinical modeling in glioblastoma patient-derived xenograft (GBM PDX) xenografts to guide clinical development of lisavanbulin-a novel tumor checkpoint controller targeting microtubules.Neuro-oncology · 2022Article
- Brain Distribution of Berzosertib: An Ataxia Telangiectasia and Rad3-Related Protein Inhibitor for the Treatment of Glioblastoma.The Journal of pharmacology and experimental therapeutics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Glioblastoma, the most lethal primary brain cancer, is extremely proliferative and invasive. Tumor cells at tumor/brain-interface often exist behind a functionally intact blood-brain barrier (BBB), and so are shielded from exposure to therapeutic drug concentrations. An ideal glioblastoma treatment needs to engage targets that drive proliferation as well as invasion, with brain penetrant therapies. One such target is the mitotic kinesin KIF11, which can be inhibited with ispinesib, a potent molecularly-targeted drug. Although, achieving durable brain exposures of ispinesib is critical for adequate tumor cell engagement during mitosis, when tumor cells are vulnerable, for efficacy. Our results demonstrate that the delivery of ispinesib is restricted by P-gp and Bcrp efflux at BBB. Thereby, ispinesib distribution is heterogeneous with concentrations substantially lower in invasive tumor rim (intact BBB) compared to glioblastoma core (disrupted BBB). We further find that elacridar-a P-gp and Bcrp inhibitor-improves brain accumulation of ispinesib, resulting in remarkably reduced tumor growth and extended survival in a rodent model of glioblastoma. Such observations show the benefits and feasibility of pairing a potentially ideal treatment with a compound that improves its brain accumulation, and supports use of this strategy in clinical exploration of cell cycle-targeting therapies in brain cancers.
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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.