Initial testing (stage 1) of the notch inhibitor PF‐03084014, by the pediatric preclinical testing program. Issue 8 (24th March 2014)

• Record Type: Journal Article
• Authors: Carol, Hernan; Maris, John M.; Kang, Min H.; Reynolds, C. Patrick; Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Wu, Jianrong; Kurmasheva, Raushan T.; Houghton, Peter J.; Smith, Malcolm A.; Lock, Richard B.
• Is Part Of: Pediatric blood & cancer. Volume 61:Issue 8(2014:Aug.)
• Page Start: 1493
• Page End: 1496
• Publication Date: 2014-03-24
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.25026
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pbc25026-sec-0001" sec-type="section"> <p>PF‐03084014, a γ‐secretase inhibitor, was tested against the PPTP <italic>in vitro</italic> cell line panel (1.0 nM to 10 μM) and against the <italic>in vivo</italic> xenograft panels (administered orally twice daily on Days 1–7 and 15–21). PF‐03084014 demonstrated limited <italic>in vitro</italic> activity, with no cell line achieving ≥50% inhibition. PF‐03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were not observed. PF‐03084014 demonstrated limited single agent activity <italic>in vitro</italic> and <italic>in vivo</italic> against the pediatric preclinical models studied. Pediatr Blood Cancer 2014; 61:1493–1496. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>