ArticleCancer chemotherapy and pharmacology2014
The selective Aurora-A kinase inhibitor MLN8237 (alisertib) potently inhibits proliferation of glioblastoma neurosphere tumor stem-like cells and potentiates the effects of temozolomide and ionizing radiation.
Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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
34 citing papers in PubMed.
- Review
- Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence.iScience · 2024Article
- Article
- vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target.Antibodies (Basel, Switzerland) · 2024Review
- Review
- Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines.Experimental and therapeutic medicine · 2023Article
- Viability fingerprint of glioblastoma cell lines: roles of mitotic, proliferative, and epigenetic targets.Scientific reports · 2021Article
- Targeting glioma cells by antineoplastic activity of reversine.Oncology letters · 2021Article
- Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives.Stem cell research & therapy · 2021Review
- Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing.American journal of cancer research · 2021Article
- Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA).Molecules (Basel, Switzerland) · 2020Article
- The therapeutic potential of Aurora kinases targeting in glioblastoma: from preclinical research to translational oncology.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Cytotoxic synergy between alisertib and carboplatin versus alisertib and irinotecan are inversely dependent on MGMT levels in glioblastoma cells.Journal of neuro-oncology · 2019Article
- Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration.Oncogene · 2019Article
- G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future.Cancer biology & medicine · 2018Article
- Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma.Neurologia medico-chirurgica · 2018Review
- Article
- Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- The CNS penetrating taxane TPI 287 and the AURKA inhibitor alisertib induce synergistic apoptosis in glioblastoma cells.Journal of neuro-oncology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
The selective Aurora-A kinase inhibitor MLN8237 is in clinical trials for hematologic malignancies, ovarian cancer and other solid tumors. We previously showed that MLN8237 is potently antiproliferative toward standard monolayer-cultured glioblastoma cells. We have now investigated the effect of MLN8237 with and without temozolomide or ionizing radiation on the proliferation of glioblastoma tumor stem-like cells (neurospheres) using soft agar colony formation assays and normal human astrocytes by MTT assay. Western blotting was utilized to compare MLN8237 IC50s to cellular Aurora-A and phosphoThr(288)Aurora-A levels. MLN8237 was more potently antiproliferative to neurosphere cells than to standard monolayer glioma cells, and was non-toxic to normal human astrocytes. Western blot analysis revealed that MLN8237 treatment inhibits phosphoThr(288)Aurora-A levels providing proof of drug target-hit in glioblastoma cells. Furthermore, phosphoThr(288)Aurora-A levels partially predicted the antiproliferative efficacy of MLN8237. We also found that Aurora-A inhibition by MLN8237 was synergistic with temozolomide and potentiated the effects of ionizing radiation on colony formation in neurosphere glioblastoma tumor stem-like cells. These results further support the potential of Aurora-A inhibitors as primary chemotherapy agents or biologic response modifiers in glioblastoma patients.
Indexed as
Identifiers
What OpenQuestion holds
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.