ArticleJournal of translational medicine2008
Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells.
Article in Journal of translational medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors.Investigational new drugs · 2016Trial
- Structure-based screening and identification of a novel Aurora-A-targeting peptide with antiproliferative activity against prostate cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- 20 years of taxane therapy in prostate cancer - the past, present and future.Nature reviews. Urology · 2026Review
- Inhibition of branched-chain alpha-keto acid dehydrogenase kinase augments the sensitivity of ovarian and breast cancer cells to paclitaxel.British journal of cancer · 2023Article
- PARP1 proximity proteomics reveals interaction partners at stressed replication forks.Nucleic acids research · 2022Article
- Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.Diagnostic pathology · 2021Article
- Mechanisms of Taxane ResistanceCancers · 2020Review
- Aurora kinases in ovarian cancer.ESMO open · 2020Review
- Wise Management of Ovarian Cancer: On the Cutting Edge.Journal of personalized medicine · 2020Review
- Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells.Theranostics · 2020Article
- G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel.Molecular and cellular biochemistry · 2019Article
- 4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion.Breast cancer research and treatment · 2019Article
- Mitotic Exit Dysfunction through the Deregulation of APC/C Characterizes Cisplatin-Resistant State in Epithelial Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Taxane-mediated radiosensitization derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX2.Oncogene · 2018Article
- Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth and improves survival in immune competent mice.Oncotarget · 2017Article
- Aurora B expression modulates paclitaxel response in non-small cell lung cancer.British journal of cancer · 2017Article
- Protective effects and mechanism of TPX2 on neurocyte apoptosis of rats in Alzheimer's disease model.Experimental and therapeutic medicine · 2017Article
- Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.Molecular cancer therapeutics · 2016Article
- TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance.Oncology letters · 2016Article
- Optimizing and predicting the in vivo activity of AT9283 as a monotherapy and in combination with paclitaxel.Journal of gastrointestinal cancer · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundA large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer. Recent data has shown that overexpression of Aurora-A can confer resistance to the taxane paclitaxel.
methodsWe used expression profiling of ovarian tumor samples to determine the most significantly overexpressed genes. In this study we sought to determine if chemical inhibition of the Aurora kinase family using VE-465 could synergize with paclitaxel to induce apoptosis in paclitaxel-resistant and sensitive ovarian cancer cells.
resultsAurora-A kinase and TPX2, an activator of Aurora-A, are two of the most significantly overexpressed genes in ovarian carcinomas. We show that inhibition of the Aurora kinases prevents phosphorylation of a mitotic marker and demonstrate a dose-dependent increase of apoptosis in treated ovarian cancer cells. We demonstrate at low doses that are specific to Aurora-A, VE-465 synergizes with paclitaxel to induce 4.5-fold greater apoptosis than paclitaxel alone in 1A9 cells. Higher doses are needed to induce apoptosis in paclitaxel-resistant PTX10 cells.
conclusionOur results show that VE-465 is a potent killer of taxane resistant ovarian cancer cells and can synergize with paclitaxel at low doses. These data suggest patients whose tumors exhibit high Aurora-A expression may benefit from a combination therapy of taxanes and Aurora-A inhibition.
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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.