{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:50:21Z","timestamp":1773658221158,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T00:00:00Z","timestamp":1191369600000},"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":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dasatinib, a dual inhibitor of the <jats:italic>src<\/jats:italic> and <jats:italic>abl<\/jats:italic> tyrosine kinases, was recently approved by the Federal Drug Administration for the treatment of imatinib mesylate\u2010resistant chronic myeloid leukemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>Dasatinib was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 0.1 nM to 1.0 \u00b5M and was tested in vivo at a dose of 50 mg\/kg administered orally twice daily 5 days per week for 4 weeks for the solid tumor xenografts and once daily for the acute lymphoblastic leukemia (ALL) xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dasatinib was selectively active against the cell lines of the PPTP in vitro panel, reaching an IC<jats:sub>50<\/jats:sub> in 6 of the 22 lines. The most sensitive were the AML line Kasumi\u20101, which has a gain\u2010of\u2010function c\u2010Kit mutation (Asn822Lys), and the rhabdoid tumor line CHLA\u2010266 (IC<jats:sub>50<\/jats:sub> approximately 10 nM for each). In the in vivo panel, dasatinib induced significant differences in EFS distribution in 8 of 32 (25%) solid tumor models and 3 of 7 ALL models. Using the time to event activity measure, dasatinib had intermediate activity against 1 of 27 (4%) evaluable solid tumor xenografts and 3 of 7 ALL xenografts. One xenograft in the ALL panel, a Philadelphia chromosome positive (Ph<jats:sup>+<\/jats:sup>) ALL xenograft, demonstrated a complete response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dasatinib was active at low nanomolar concentrations against a small subset of the PPTP's in vitro panel. Dasatinib had limited in vivo activity against the PPTP solid tumor xenografts, but was highly active against a Ph<jats:sup>+<\/jats:sup> ALL xenograft and also had anti\u2010leukemia activity against two other xenografts. Pediatr Blood Cancer 2008;50:1198\u20131206. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.21368","type":"journal-article","created":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T19:46:59Z","timestamp":1191440819000},"page":"1198-1206","source":"Crossref","is-referenced-by-count":66,"title":["Initial testing of dasatinib by the pediatric preclinical testing program"],"prefix":"10.1002","volume":"50","author":[{"given":"E. 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