ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- Trial
- An open-label, single-arm, phase 2 study of the Aurora kinase A inhibitor alisertib in patients with advanced urothelial cancer.Investigational new drugs · 2016Trial
- Dna aneuploidy and urothelial carcinoma: A meta-analysis.Current therapeutic research, clinical and experimental · 2026Review
- A molecular landscape tracking the progression of non-muscle invasive bladder cancer.World journal of urology · 2026Review
- Article
- Dual Targeting of Aurora-A and Bcl-xL Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer.Cancer science · 2025Article
- Article
- Alisertib exerts KRAS allele‑specific anticancer effects on colorectal cancer cell lines.Experimental and therapeutic medicine · 2023Article
- Rad54L promotes bladder cancer progression by regulating cell cycle and cell senescence.Medical oncology (Northwood, London, England) · 2022Article
- A phase I dose escalation, dose expansion and pharmacokinetic trial of gemcitabine and alisertib in advanced solid tumors and pancreatic cancer.Cancer chemotherapy and pharmacology · 2022Article
- Article
- MicroRNA-363-3p, negatively regulated by long non-coding RNA small nucleolar RNA host gene 5, inhibits tumor progression by targeting Aurora kinase A in colorectal cancer.Bioengineered · 2022Article
- Screening and identification of hub genes in bladder cancer by bioinformatics analysis and KIF11 is a potential prognostic biomarker.Oncology letters · 2021Article
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Insights into the non-mitotic functions of Aurora kinase A: more than just cell division.Cellular and molecular life sciences : CMLS · 2020Review
- BORA regulates cell proliferation and migration in bladder cancer.Cancer cell international · 2020Article
- Article
- Relationship between Aurora-A V57I Polymorphism and the Risk of Cancer: A Meta-Analysis and Trial Sequential Analysis.Journal of Cancer · 2020Review
- Genetic variant of MAML2 in the NOTCH signaling pathway and the risk of bladder cancer: A STROBE-compliant study.Medicine · 2020Observational
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeDespite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target. EXPERIMENTAL
designGene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model.
resultsA set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared with normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell-cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells.
conclusionsMitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer.
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