ArticleMolecular and cellular biology2007
MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and chromosome congression defects leading to aneuploidy.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01848067 (A Phase I/II Study of Alisertib in Combination With Abiraterone and Prednisone for Patients With Castration-Resistant Prostate Cancer After Progression on Abiraterone), which is not on this map. Cited by 107 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.
A Phase I/II Study of Alisertib in Combination With Abiraterone and Prednisone for Patients With Castration-Resistant Prostate Cancer After Progression on Abiraterone
Who cites it
107 citing papers in PubMed, 202 citations in OpenAlex.
- Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor.Neuro-oncology · 2023Trial
- Efficacy and Safety of Weekly Paclitaxel With or Without Oral Alisertib in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial.JAMA network open · 2021Trial
- A Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma.The oncologist · 2020Trial
- Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Therapy-induced senescence rewires the melanoma secretome to promote antitumor immune response and augment cell therapies.Journal for immunotherapy of cancer · 2026Article
- KRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors.NPJ precision oncology · 2026Article
- Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.Angewandte Chemie (International ed. in English) · 2025Article
- MAP4 phosphorylation induced by ARID1A loss sensitizes colorectal cancer cells to EMP.Cell death & disease · 2025Article
- Article
- Targeting AURKA to induce synthetic lethality in CREBBP-deficient B-cell malignancies via attenuation of MYC expression.Oncogene · 2024Article
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- The role of Golgi complex proteins in cell division and consequences of their dysregulation.Frontiers in cell and developmental biology · 2024Review
- Development and therapeutic evaluation of 5D3(CC-MLN8237)Frontiers in pharmacology · 2024Article
- Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.Journal of experimental & clinical cancer research : CR · 2023Review
- PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size.The Journal of cell biology · 2023Article
- EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly.iScience · 2023Article
- Design, synthesis, and evaluation of a novel PET imaging agent targeting lipofuscin in senescent cells.RSC advances · 2022Article
- Review
- Structural Organization and Function of the Golgi Ribbon During Cell Division.Frontiers in cell and developmental biology · 2022Article
- Chromosome oscillation promotes Aurora A-dependent Hec1 phosphorylation and mitotic fidelity.The Journal of cell biology · 2021Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aurora A kinase plays an essential role in the proper assembly and function of the mitotic spindle, as its perturbation causes defects in centrosome separation, spindle pole organization, and chromosome congression. Moreover, Aurora A disruption leads to cell death via a mechanism that involves aneuploidy generation. However, the link between the immediate functional consequences of Aurora A inhibition and the development of aneuploidy is not clearly defined. In this study, we delineate the sequence of events that lead to aneuploidy following Aurora A inhibition using MLN8054, a selective Aurora A small-molecule inhibitor. Human tumor cells treated with MLN8054 show a high incidence of abnormal mitotic spindles, often with unseparated centrosomes. Although these spindle defects result in mitotic delays, cells ultimately divide at a frequency near that of untreated cells. We show that many of the spindles in the dividing cells are bipolar, although they lack centrosomes at one or more spindle poles. MLN8054-treated cells frequently show alignment defects during metaphase, lagging chromosomes in anaphase, and chromatin bridges during telophase. Consistent with the chromosome segregation defects, cells treated with MLN8054 develop aneuploidy over time. Taken together, these results suggest that Aurora A inhibition kills tumor cells through the development of deleterious aneuploidy.
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.