{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:35:23Z","timestamp":1791297323492,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,1,27]],"date-time":"2010-01-27T00:00:00Z","timestamp":1264550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>MLN8237 was tested against the Pediatric Preclinical Testing Program (PPTP) <jats:italic>in vitro<\/jats:italic> panel at concentrations ranging from 1.0\u2009nM to 10\u2009\u00b5M and was tested against the PPTP <jats:italic>in vivo<\/jats:italic> panels at a dose of 20\u2009mg\/kg administered orally twice daily\u2009\u00d7\u20095 days. Treatment duration was 6 weeks for solid tumor xenografts and 3 weeks for ALL xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MLN8237 had a median IC<jats:sub>50<\/jats:sub> of 61\u2009nM against the PPTP <jats:italic>in vitro<\/jats:italic> panel. The ALL cell lines were more sensitive and the rhabdomyosarcoma cell lines less sensitive than the remaining PPTP cell lines. <jats:italic>In vivo<\/jats:italic>, MLN8237 induced significant differences in event\u2010free survival (EFS) distributions compared to controls in 32\/40 (80%) solid tumor models and all (6\/6) ALL models. Maintained complete responses (CRs) were observed in 3 of 7 neuroblastoma xenografts, and all 6 evaluable ALL xenografts achieved CR (n\u2009=\u20094) or maintained CR (n\u2009=\u20092) status. Maintained CRs were observed among single xenografts in other panels, including the Wilms tumor, rhabdoid tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and medulloblastoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:italic>in vivo<\/jats:italic> activity observed against the neuroblastoma panel far exceeds that observed for standard agents evaluated against the panel by the PPTP. High levels of <jats:italic>in vivo<\/jats:italic> activity were also observed against the ALL xenograft panel. These data support expedited clinical development of MLN8237 in childhood cancer. Pediatr Blood Cancer 2010;55:26\u201334. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.22430","type":"journal-article","created":{"date-parts":[[2010,1,27]],"date-time":"2010-01-27T20:41:12Z","timestamp":1264624872000},"page":"26-34","source":"Crossref","is-referenced-by-count":205,"title":["Initial testing of the aurora kinase a inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP)"],"prefix":"10.1002","volume":"55","author":[{"given":"John M.","family":"Maris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gorlick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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