{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T14:34:56Z","timestamp":1778337296067,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:00:00Z","timestamp":1340841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010C was established, suggesting that Aurora A inhibition may be a promising strategy to increase the efficacy of ara\u2010C. Accordingly, alisertib significantly potentiated the antileukemic activity of ara\u2010C in both AML cell lines and primary blasts. Targeted FOXO3a knockdown significantly blunted the pro\u2010apoptotic effects of the alisertib\/ara\u2010C combination, indicating that it is an important regulator of sensitivity to these agents. <jats:italic>In vivo<\/jats:italic> studies demonstrated that alisertib significantly augmented the efficacy of ara\u2010C 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\u2010C that warrants further investigation.<\/jats:p>","DOI":"10.1002\/ijc.27579","type":"journal-article","created":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T11:40:21Z","timestamp":1333626021000},"page":"2693-2703","source":"Crossref","is-referenced-by-count":46,"title":["Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO\u2010dependent mechanism"],"prefix":"10.1002","volume":"131","author":[{"given":"Kevin R.","family":"Kelly","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffan T.","family":"Nawrocki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia 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