ArticleJournal of cellular and molecular medicine2011
The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic myeloid leukaemia and significantly increases the efficacy of nilotinib.
Article in Journal of cellular and molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia.Leukemia · 2013Trial
- A Novel Aurora Kinase Inhibitor Attenuates Leukemic Cell Proliferation Induced by Mesenchymal Stem Cells.Molecular therapy oncolytics · 2020Article
- Insights into the non-mitotic functions of Aurora kinase A: more than just cell division.Cellular and molecular life sciences : CMLS · 2020Review
- Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in gastrointestinal cancer.Investigational new drugs · 2019Article
- Management of Chronic Myeloid Leukemia in Advanced Phase.Frontiers in oncology · 2019Review
- Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells.International journal of molecular sciences · 2018Review
- 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
- Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia.Molecular cancer · 2018Review
- Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques.Scientific reports · 2017Article
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- BIRC6 mediates imatinib resistance independently of Mcl-1.PloS one · 2017Article
- Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.Scientific reports · 2016Article
- The Aurora kinase inhibitors in cancer research and therapy.Journal of cancer research and clinical oncology · 2016Review
- Recent advances in the development of Aurora kinases inhibitors in hematological malignancies.Therapeutic advances in hematology · 2015Review
- Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review.Journal of clinical medicine research · 2015Review
- 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
- Aurora kinase A in gastrointestinal cancers: time to target.Molecular cancer · 2015Review
- Issues in interpreting the in vivo activity of Aurora-A.Expert opinion on therapeutic targets · 2015Review
- The aurora kinases in cell cycle and leukemia.Oncogene · 2015Review
- Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer.Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel therapies are urgently needed to prevent and treat tyrosine kinase inhibitor resistance in chronic myeloid leukaemia (CML). MLN8237 is a novel Aurora A kinase inhibitor under investigation in multiple phase I and II studies. Here we report that MLN8237 possessed equipotent activity against Ba/F3 cells and primary CML cells expressing unmutated and mutated forms of breakpoint cluster region-Abelson kinase (BCR-ABL). Notably, this agent retained high activity against the T315I and E255K BCR-ABL mutations, which confer the greatest degree of resistance to standard therapy. MLN8237 treatment disrupted cell cycle kinetics, induced apoptosis, caused a dose-dependent reduction in the expression of the large inhibitor of apoptosis protein Apollon, and produced a morphological phenotype consistent with Aurora A kinase inhibition. In contrast to other Aurora kinase inhibitors, MLN8237 did not significantly affect BCR-ABL activity. Moreover, inhibition of Aurora A with MLN8237 significantly increased the in vitro and in vivo efficacy of nilotinib. Targeted knockdown of Apollon sensitized CML cells to nilotinib-induced apoptosis, indicating that this is an important factor underlying MLN8237's ability to increase the efficacy of nilotinib. Our collective data demonstrate that this combination strategy represents a novel therapeutic approach for refractory CML that has the potential to suppress the emergence of T315I mutated CML clones.
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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.