ArticleInternational journal of cancer2012
Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial.The Lancet. Haematology · 2020Trial
- Trial
- Collaborative effect of Csnk1a1 haploinsufficiency and mutant p53 in Myc induction can promote leukemic transformation.Blood advances · 2024Article
- FOXO3a-interacting proteins' involvement in cancer: a review.Molecular biology reports · 2024Review
- Article
- Design and Synthesis of a Novel 4-aryl-N-(2-alkoxythieno [2,3-Pharmaceuticals (Basel, Switzerland) · 2022Article
- Chromosomal Instability in Acute Myeloid Leukemia.Cancers · 2021Review
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?Journal of hematology & oncology · 2019Review
- Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches.Therapeutic advances in hematology · 2019Review
- Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells.International journal of molecular sciences · 2018Review
- Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.Cancer research · 2017Review
- Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia.Haematologica · 2017Article
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.Molecular cancer therapeutics · 2016Article
- Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose.Investigational new drugs · 2015Article
- Alisertib (MLN8237), a selective Aurora-A kinase inhibitor, induces apoptosis in human tongue squamous cell carcinoma cell both in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- The aurora kinases in cell cycle and leukemia.Oncogene · 2015Review
- The NEDD8-activating enzyme inhibitor MLN4924 disrupts nucleotide metabolism and augments the efficacy of cytarabine.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Aurora Kinase Inhibitors: Current Status and Outlook.Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Novel therapies are urgently needed to improve clinical outcomes for patients with acute myeloid leukemia (AML). The investigational drug alisertib (MLN8237) is a novel Aurora A kinase inhibitor being studied in multiple Phase I and II studies. We investigated the preclinical efficacy and pharmacodynamics of alisertib in AML cell lines, primary AML cells and mouse models of AML. Here, we report that alisertib disrupted cell viability, diminished clonogenic survival, induced expression of the FOXO3a targets p27 and BIM and triggered apoptosis. A link between Aurora A expression and sensitivity to ara-C was established, suggesting that Aurora A inhibition may be a promising strategy to increase the efficacy of ara-C. Accordingly, alisertib significantly potentiated the antileukemic activity of ara-C in both AML cell lines and primary blasts. Targeted FOXO3a knockdown significantly blunted the pro-apoptotic effects of the alisertib/ara-C combination, indicating that it is an important regulator of sensitivity to these agents. In vivo studies demonstrated that alisertib significantly augmented the efficacy of ara-C without affecting its pharmacokinetic profile and led to the induction of p27 and BIM. Our collective data indicate that targeting Aurora A with alisertib represents a novel approach to increase the efficacy of ara-C that warrants further investigation.
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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.